e18626 Background: Pts with malignancies are at risk for developing severe complications of COVID-19 with high mortality rate. We retrospectively analyzed COVID-19 related outcomes for hospitalized pts with SMs. Methods: We collected data on hospitalized pts with SMs and COVID-19 from 3/1/20 to Jan 1/1/21. Diagnosis COVID-19 was confirmed by RT-PCR of nasopharyngeal swabs. We assessed the association between the 30-day mortality and potential prognostic variables such as tumor types, cancer status, timing of treatment, types of anticancer therapy using logistic regression analyses. Results: A total of 246 hospitalized pts with SMs had COVID-19. Median age was 70 years, 87 (35%) were ≥75 years, 151 (61%) were female. The most common SMs were breast (56 [23%]), non-small cell lung (44 [18%]) and colon (31 [13%]). 154 (63%) pts were on active anticancer therapies. Of those 88 (35.5%) received treatment within 2 weeks, 16 (16.5%) within 4-12 weeks, 99 (39.9%) >3 months prior to COVID-19 diagnosis. 101 (65%) pts received cytotoxic chemotherapies, 26 (16.8%) received immune check point inhibitors (ICIs), 17 (11%) received targeted agents such as anti-EGFR therapy and 11 (7.1%) received monoclonal antibodies. Overall 30-day mortality was 42%, however, all pts with melanoma (7/7) died. The 30-day mortalities for pts who received anticancer treatments within 4 weeks, 4-12 weeks and >12 weeks of COVID-19 diagnosis were 47%, 50%, and 37%. For pts who never received treatment, 30-day mortality was 31%. For pts were in remission, stable disease and progressive disease, the 30-day mortalities were 32%, 35% and 62%. The 30-day mortalities for pts who received cytotoxic therapy, monoclonal antibodies, targeted therapies and ICIs, were 38%, 46%, 41% and 69%. Logistic regression analysis showed that pts who were >80 years of age (OR 3.6, 95% CI 1.6-8.1), had progressive disease (OR 3.4, 95% CI 1.8-6.5) or treated with ICIs (OR 3.6, 95% CI 1.5-8.7) were associated with higher 30-day mortality. Conclusions: COVID-19 associated 30-day mortality is high for hospitalized pts with SMs. Early surveillance of clinical deterioration could be helpful for hospitalized SMs pts with risk factors identified here. Further studies are needed to discern the observed association between ICIs use and worse COVID-19 outcome.[Table: see text]