Data on clinical manifestations of COVID-19 in immunocompromised patients in Russia is lacking, which prompted us to conduct a study to investigate clinical manifestations, risk factors, and outcomes of SARS-CoV-2 infection in children with oncological and hematological diseases treated at the D. Rogachev NMRCPHOI (Center). In this retrospective-prospective, nonrandomized, non-interventional study we enrolled children under 18 years with cancer, hematologic malignancies, and primary immunodeficiencies (PIDs) who underwent treatment at the Center from April 2020 to October 2021. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe and critical. The study was approved by the Independent Ethics Committee and the Scientific Council of the Center. The study included 89 patients with a median age of 9.7 years and almost equal gender distribution (the male-to-female ratio was 1.1:1). Most patients (74%) were infected in a family claster. The main underlying diseases were: hemoblastoses (43.8%), solid tumors (33.7%), PIDs (14.6%). The most common clinical symptoms were fever (29%) and respiratory symptoms (47%). In 79% of cases, patients were asymptomatic or had mild symptoms; 21% of patients had moderate and severe disease (16% and 5%, accordingly). Risk factors associated with severe COVID-19 included lymphopenia (p < 0.001) and hematopoietic stem cell transplantation (HSCT) (p = 0.002). Full recovery was documented in 84% of the patients, 16% died, however COVID-attributed mortality was 5.5%. The highest mortality was in patients with moderate/severe COVID-19 (47% vs 7%, p < 0.001), in those with progression/ relapse of the underlying disease (36.3% vs 6%, p = 0.02), in children who had received specific therapy within a year before the SARS-CoV-2 diagnosis (21% vs 0%, p = 0.02), among HSCT recipients (31.6% vs 12.1%, p = 0.02), and patients with concomitant infections (33% vs 9.2%, p < 0.01). Factors associated with poor prognosis were moderate or severe COVID-19, relapse/ progression of the underlying disease, specific treatment (HSCT in particular) within 1 year before the SARS-CoV-2 diagnosis, concomitant infections, and lymphopenia. Data obtained in this study can help physicians with management decisions at this population of patients.