Introduction: Following the acute phase of respiratory illness caused by the SARS-CoV-2 virus, a significant number of patients report persistent fatigue. Fatigue is considered debilitating and disabling, affecting quality of life, work performance, and social/familial relationships. Multicomponent exercise prescription and dosage in its various forms has proven to be a preventive and therapeutic strategy in numerous medical conditions. However, to date, evidence regarding its effect on fatigue secondary to SARS-CoV-2 infection remains scarce. Objective: To evaluate the effect of a multicomponent exercise program on self-perceived fatigue, aerobic capacity, lower-limb muscle strength, body fat percentage, and muscle mass in individuals aged 30 to 60 years with history of COVID-19.

Methodology: A quasi-experimental study (pretest-posttest trial) included 15 individuals reporting fatigue via the Fatigue Severity Scale (FSS) and with a history of more than 12 weeks post-SARS-CoV-2 infection. All participants completed a 12-week multicomponent exercise program. The primary outcome was a reduction in fatigue perception. Secondary outcomes included aerobic capacity, lower-limb muscle strength, body fat percentage, and muscle mass. Results: Self-perceived fatigue decreased by 2.5 points (95% CI: 1.7–3.2; p = 0.001). Aerobic capacity increased by 10.8 mL/kg/min (95% CI: 5.7–19.9; p = 0.006). No statistically significant changes were observed in muscle strength, body fat percentage, or muscle mass at the end of the follow-up period. Conclusions: The multicomponent exercise program for reducing post-COVID-19 self-perceived fatigue can be considered an effective tool for managing post-COVID-19 sequelae in populations with persistent symptoms who have not received prior treatment.