This randomized crossover clinical trial aimed to assess post-exertional symptoms in patients with post-COVID condition (PCC) and to investigate the physiologic mechanisms underlying PCC. The study included 31 non-hospitalized patients with PCC and 31 age- and sex-matched healthy controls. Participants completed three types of exercise (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order, with symptoms assessed at baseline, immediately after exercise, and 48 hours post-exercise. The primary outcome was the difference in changes in fatigue symptoms from baseline to 48 hours post-exercise, measured using the visual analog scale (VAS). Key findings include: - Patients with PCC reported more symptoms than controls at all time points. - There was no significant difference in symptom worsening between the groups after any type of exercise. - Patients with PCC had greater exacerbation of muscle pain after HIIT and concentration difficulties after MICT compared to controls. - At baseline, patients with PCC showed preserved lung and heart function but had lower aerobic capacity and less muscle strength compared to controls. - 62% of patients with PCC showed myopathic signs, and 13% had postural orthostatic tachycardia. The study suggests that cautious exercise rehabilitation should be recommended to prevent further deconditioning among patients with PCC. The findings indicate that while exercise was generally well-tolerated, patients with PCC may benefit from individualized exercise programs to enhance physical function and counteract muscle deconditioning.This randomized crossover clinical trial aimed to assess post-exertional symptoms in patients with post-COVID condition (PCC) and to investigate the physiologic mechanisms underlying PCC. The study included 31 non-hospitalized patients with PCC and 31 age- and sex-matched healthy controls. Participants completed three types of exercise (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order, with symptoms assessed at baseline, immediately after exercise, and 48 hours post-exercise. The primary outcome was the difference in changes in fatigue symptoms from baseline to 48 hours post-exercise, measured using the visual analog scale (VAS). Key findings include: - Patients with PCC reported more symptoms than controls at all time points. - There was no significant difference in symptom worsening between the groups after any type of exercise. - Patients with PCC had greater exacerbation of muscle pain after HIIT and concentration difficulties after MICT compared to controls. - At baseline, patients with PCC showed preserved lung and heart function but had lower aerobic capacity and less muscle strength compared to controls. - 62% of patients with PCC showed myopathic signs, and 13% had postural orthostatic tachycardia. The study suggests that cautious exercise rehabilitation should be recommended to prevent further deconditioning among patients with PCC. The findings indicate that while exercise was generally well-tolerated, patients with PCC may benefit from individualized exercise programs to enhance physical function and counteract muscle deconditioning.