This study aimed to investigate the role of the thymus in influencing long-term outcomes of COVID-19 by comparing the thymic appearance in patients with and without COVID-19 pulmonary sequelae at chest computed tomography (CT). A total of 102 adult patients previously hospitalized for COVID-19 underwent a follow-up chest CT three months after discharge. Pulmonary sequelae and thymic appearance were independently assessed by two experienced radiologists. The thymus was detectable in 55/102 patients (54%), with only 7/55 (13%) having any kind of pulmonary sequelae, compared to 33 out of 47 (70%, p < 0.001) in patients without thymic visibility, as confirmed in age-stratified analysis and at logistic regression analysis, where thymic involution had a 9.3 odds ratio (95% CI 3.0–28.2, p < 0.001) for the development of pulmonary sequelae. These results support the hypothesis that thymic reactivation plays a protective role against adverse long-term outcomes of COVID-19.