Low levels of testosterone may lead to reduced diaphragm excursion and inspiratory time during COVID-19 infection. We report the case of a 38-year-old man with a positive result on a reverse transcriptase-polymerase chain reaction test for SARS-CoV-2, admitted to the intensive care unit with acute respiratory failure. After several days on mechanical ventilation and use of rescue therapies, during the weaning phase, the patient presented dyspnea associated with low diaphragm performance (diaphragm thickness fraction, amplitude, and the excursion-time index during inspiration were 37%, 1.7 cm, and 2.6 cm/s, respectively) by ultrasonography and reduced testosterone levels (total testosterone, bioavailable testosterone and sex hormone binding globulin (SHBG) levels were 9.3 ng/dL, 5.8 ng/dL, and 10.5 nmol/L, respectively). Testosterone was administered three times 2 weeks apart (testosterone undecanoate 1000 mg/4 mL intramuscularly). Diaphragm performance improved significantly (diaphragm thickness fraction, amplitude, and the excursion-time index during inspiration were 70%, 2.4 cm, and 3.0 cm/s, respectively) 45 and 75 days after the first dose of testosterone. No adverse events were observed, although monitoring was required after testosterone administration. Testosterone replacement therapy led to good diaphragm performance in a male patient with COVID-19. This should be interpreted with caution due to the exploratory nature of the study.