Coronavirus-disease 2019 (COVID-19) affects the respiratory system with high morbidity in elderly and comorbid patients. Acute COVID-19 infection (CI) primarily leads to respiratory failure, long-term effects on respiratory skeletal muscle however remain vague. Thus, histopathological marker expression of oxidative stress, inflammation, satellite cell activity, myosin fiber composition, and cellular senescence were analyzed in intercostal muscle and diaphragm to compare respiratory muscle degeneration (RMD) in deceased CI-positive and control patients. Beside CI, the impact of BMI, age, sex, ventilation status, and duration of hospitalization on RMD were evaluated. CI-positive patients exhibited higher numbers of regenerative stem cells, but no association between CI status and RMD was observed. Interestingly, ventilation support and lung-associated comorbidities had no effect on expression of RMD markers (p > 0.05). However, intercostal muscle showed BMI-dependent changes in expression of RMD markers, regardless of the CI status, with increased cytokine expression (p = 0.04), reduced antioxidative capacity (p = 0.05), and low stem cell prevalence (p = 0.02) in patients with high BMI. Moreover, elderly patients demonstrated increased oxidative stress (p = 0.001) and cell senescence (p = 0.03) independent of CI status. Notably, immobility drives muscle fiber transformation to Myosin ST (p = 0.03), since prolonged hospitalization correlated with muscle fiber type shift. Limitations included incomplete retrospective data collection and absence of adequate samples for molecular analyses. Together, RMD is influenced by BMI, age and immobility rather than the CI status alone. Future studies including larger cohorts, molecular analyses, and evaluation of patient data in addition to CI status alone, will further support meaningful analyses and interpretation of RMD and its impact on post CI recovery.