Experts have called attention to the possible negative impact of the coronavirus disease 2019 (COVID-19)-related cytokine storm syndrome on the progression of leprosy-related disabilities. We assessed the frequency of reactional states in patients co-infected with Mycobacterium leprae and severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2). We consecutively included patients during the first peak of the COVID-19 epidemic in Brazil and analyzed the expressions of genes encoding interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12A, IL-12B, and tumor necrosis factor-α in peripheral blood mononuclear cells. We included 64 leprosy patients and 50 controls. Twelve of the leprosy patients and 14 of the controls had been diagnosed with COVID-19. Co-infection was associated with increased IL-6 (P = 0.043) and IL-12B (P = 0.017) expression. The median disability grades were higher for leprosy/COVID-19 patients; however, the difference was not significant (P = 0.194). Patients co-infected with M. leprae and SARS-CoV-2 may experience a higher-grade proinflammatory state.