Background: Immune checkpoint inhibitor (atezolizumab or durvalumab) combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase III clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC, excluded patients with an Eastern Cooperative Group (ECOG) Performance Status (PS) of Two or Greater. Therefore, data on efficacy of this combination in this subgroup of ES-SCLC patients whose performance status two or greater is limited. Methods: A retrospective analysis was performed of patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, ECOG-PS, date of diagnosis, date of progression, whole brain radiation, CNS involvement, liver involvement, stereotactic body radiation, chest consolidation, platinum sensitivity, lines of therapy and last follow up date were extracted. Overall Survival (OS) and progression free survival (PFS) for ECOG-PS 2-3 were compared to patients with an ECOG-PS 0-1. Results: A total of 84 patients were identified with a median age of 68.2 (48-88) years old. Of these, 54 patients were identified with an ECOG-PS 0-1 and 30 patients with an ECOG-PS 2-3. The median PFS for the ECOG PS 0-1 cohort was 5.2 months (95% CI 4.6-6.1) while the median PFS for the ECOG-PS 2-3 cohort was 6.0 months (95% CI 4.2-7.7; logrank p = 0.93). The median OS for the ECOG-PS 0-1 cohort was 10.8 months (95% CI 8.5-12.9) while the median OS for the ECOG-PS 2-3 cohort was 10.3 months (95% CI 6.0-14.1; logrank p = 0.39). Hazard ratios of ECOG-PS 0-1 versus 2-3 showed no tendency of increased PFS or OS for either group within cox proportional hazards models. Forty-three percent of ECOG-PS 0-1 achieved a partial response (PR) and 57% of patients who had ECOG-PS 2-3 also achieved a PR (Fisher’s exact p = 0.23). A complete response was found in 4% of ECOG-PS 0-1 compared to 3% in the ECOG-PS 2-3 cohort. For patients who responded to initial therapy, 46% of ECOG-PS 2-3 patients had a platinum sensitive relapse while only 33% of ECOG-PS 0-1 were still platinum sensitive at the time of relapse. Five ECOG-PS 2-3 patients were able to receive a second-line therapy. Conclusions: To our knowledge, this is the first study to evaluate chemoimmunotherapy in the subgroup of ES-SCLC patients with an ECOG-PS 2 or greater. This retrospective study demonstrated no significant difference in PFS, OS, and ability to achieve a least a PR in ECOG-PS 2-3 cohort when compared to ECOG-PS 0-1. Therefore, chemoimmunotherapy should not be reserved for only an ECOG-PS of 0-1 but should be considered for all treatment eligible patients.