Why Energy Feels Broken in ME/CFS and Long COVID and the Importance of Pacing

If you live with ME/CFS or Long COVID, you already know the most frustrating part isn’t just fatigue. It’s the way your body seems to punish you for doing things that used to be normal. A short walk, a conversation, standing in a queue, even thinking too hard, and hours or days later, everything crashes.

This delayed worsening of symptoms is called post-exertional malaise (PEM), and it is the defining feature of these illnesses. But understanding why it happens and why some people slowly improve while others don’t can help make sense of what your body is doing and why pacing matters so much.

This Is a Biological Illness — Not “Just Fatigue”

PEM is not due to laziness or a lack of motivation. It is a biological reaction to exertion where symptoms worsen hours or days after activity. This delayed response suggests that the body’s energy systems are struggling to recover after even mild stress (1).

The Energy Problem at the Cellular Level

Our cells produce energy through mitochondria, tiny organelles that convert nutrients and oxygen into ATP (adenosine triphosphate), the energy currency of the cell.

In healthy people:

• The mitochondria adjust to different fuel types

• They ramp up energy production quickly when needed

• They recover efficiently after exertion

In ME/CFS and Long COVID, research shows:

• Mitochondrial energy production is disrupted

• Recovery after exertion is inefficient

• Metabolites build up abnormally after activity

  
  

Several studies have shown that people with ME/CFS have altered metabolic profiles both at rest and after exercise, indicating a disrupted energy response and recovery pattern compared with healthy controls (1). 

What Is Metabolic Inflexibility?

Metabolic inflexibility means the body cannot smoothly switch between fuel sources (glucose and fat) depending on what’s needed. Instead, it gets stuck, often relying prematurely on low-yield, less efficient energy pathways.

In healthy metabolism:

• Cells use glucose first

• If demand continues, they shift to fats

• After exertion, they return to baseline

  
  

In ME/CFS and Long COVID:

• This shift is impaired

• Some metabolites accumulate in blood after exertion

• Fats and other fuels are used inefficiently

  
  

A modelling study comparing muscle metabolism in ME/CFS and Long COVID found shared metabolic irregularities, indicating overlapping dysfunction in how energy pathways are regulated (2). 

This supports the concept of metabolic inflexibility, where the body cannot adjust fuel use in response to exertion or recovery demands.

Why PEM Happens (Especially Delayed Symptoms)

Most people with ME/CFS and Long COVID experience PEM several hours to days after exertion. This is puzzling at first but it makes sense when you look at what’s happening metabolically:

1. Exertion increases ATP demand.

   Your cells try to make more energy.

   
   

2. Mitochondria in ME/CFS/Long COVID are impaired.

   Some pathways that convert fuel into ATP are less efficient, so less energy is made and by-products (like lactate) accumulate (3). 

   
   

3. After activity ends, your cells struggle to recover.

   Energy production remains low, cellular stress markers stay elevated, and inflammation persists, leading to worsening symptoms hours or days later.

   
   

This creates a sort of “metabolic debt”, the system simply cannot bounce back like it should.

How PEM Affects Different Body Systems

Symptoms can vary widely, depending on which energy-dependent system is stressed.

1. Orthostatic Intolerance & Blood Pressure Control

Standing upright demands a lot of energy — your nervous system is constantly adjusting heart rate and blood vessel tone to keep blood flowing to the brain. When mitochondria and autonomic regulation are impaired:

• Blood pools in the lower body

• Brain gets less oxygen

• Heart rate compensation becomes inefficient

• Symptoms worsen hours / days after exertion

  
  

This is why standing can feel worse after a crash, it’s an energy failure in the systems that maintain circulation. This is why strategies like pacing, fluids, and salt (when appropriate) help many patients.

2. Brain Fog & Cognitive Dysfunction

Your brain consumes a huge amount of ATP — far more than other organs. Neurons don’t have much backup energy capacity, so when mitochondrial energy production falters:

• Synaptic activity slows

• Memory and concentration get foggy

• Thinking feels heavy

  
  

Metabolomic studies show altered pathways in cerebrospinal fluid linked to energy metabolism in ME/CFS, supporting real metabolic disruption rather than “just fatigue.” (4)

3. Muscle Fatigue & Pain

Muscle energy metabolism also appears altered in ME/CFS:

• After exertion, pathways that should process fuel efficiently are disrupted

• Lactate and intermediate metabolites accumulate early

• Muscles feel heavy, weak, or painful after activity

  
  

These changes are seen in plasma metabolomics following exercise challenges, demonstrating that metabolic response and recovery are different in ME/CFS. (1)

Why Some People Improve While Others Don’t

This is a big question and doctors often can’t predict exactly who will recover and who won’t, but research and clinical experience suggest recovery depends on how multiple systems interact over time.

Recovery Requires Three Things to Reset:

To slowly improve, your body must:

1. Repair or adapt mitochondrial pathways

2. Down-regulate persistent immune activation

3. Restore autonomic nervous system flexibility

   
   

If even one of these stays stuck, progress stalls.

1. Severity of Initial Mitochondrial Disruption

Some people have mainly functional metabolic dysregulation (often reversible), while others may have deeper or structural changes that take longer to resolve.

Some studies find reduced ATP production and disrupted energy pathways in ME/CFS, supporting the idea that mitochondrial and metabolic dysfunction are central to symptoms (5).

2. Immune Activation Can Become Self-Perpetuating

Ongoing immune signals can suppress mitochondrial function and keep the system in a stressed state. This feedback loop between immune activation and metabolism seems to play a role in some people with long COVID and ME/CFS alike (6). 

3. Autonomic Nervous System

Even when energy production improves, the nervous system that controls heart rate, blood pressure, and vascular tone may remain dysregulated. Persistent autonomic dysfunction reduces overall energy efficiency, slowing recovery.

4. Repeated Crashes Slow Healing

Every episode of PEM is not just a symptom, it creates additional metabolic stress. This makes it harder for the system to rebuild because it never gets a stable period of recovery.

This is why pacing, avoiding PEM, is a therapeutic approach, not a concession.

Why Supporting the Mitochondria Has to Be Done Carefully

Many people instinctively try to “boost energy” with:

• Exercise

• Stimulants

• High-dose supplements

  
  

But in ME/CFS/Long COVID, mitochondria are not just low on fuel, they’re not processing fuel efficiently. Pushing them harder can paradoxically worsen PEM.

Instead, support should be:

• Preventive (reduce demand)

• Protective (reduce oxidative stress)

• Gradual (small steps, long rest)

  
  

The most effective support strategies include:

• Reduce demand (pacing)

• Support repair (sleep, nutrition, gentle movement)

• Avoid repeated overload

• Use supplements cautiously and gradually

  
  

Until underlying dysfunction resolves, forcing adaptation, as in typical exercise training, can be harmful.

A New Way to Understand Recovery

Recovery is not linear. It’s not “more effort = progress.” It’s more like:

Recovery happens when your body finally has enough spare energy to rebuild itself.

You may see:

• Longer stable periods

• Smaller or less severe crashes

• Small increases in tolerated activity -  a gradual widening of your energy envelope

• Increased tolerance for standing, thinking, or gentle movement

• More predictable PEM triggers

  
  

These are real signs of metabolic pathways regaining flexibility and resilience.

Final Thoughts:

ME/CFS and Long COVID are illnesses of energy regulation, not character.

Your limits are real. Your symptoms are biological. Your body is not broken, it is protecting itself in a system under strain.

Understanding what’s happening doesn’t magically fix it, but it can:

• Reduce self-blame

• Clarify why pacing matters

• Help you recognize real progress

• Push back against harmful advice

  
  

And perhaps most importantly, it reminds you that needing rest is not failure - it’s physiology.