Background: Cemiplimab is a first PD1 inhibitor for treatment of locally advanced cutaneous squamous cell carcinoma (laSCC) and metastatic SCC (mSCC). The purpose of this study is to report outcomes of patients with SCC, treated with cemiplimab in routine clinical practice in Slovenia in twenty-month period. Methods: In this retrospective cohort study we analyzed medical records of patients with laSCC and mSCC inappropriate for surgery or radiotherapy treated with cemiplimab in first line between May 2020 and November 2022. The baseline characteristics, outcomes, immune related adverse events (irAE). Results: 28 patients were included, 24 with laSCC and 4 with mSCC, with a median age of 76.1 years. Of them, 18 % (5 patients) a concomitant autoimmune disease. The estimated median progression-free survival (PFS) was 4.4 months (95% CI: 1.5–7.3). The median overall survival (OS) was 7.3 months (95% CI: 4.6–9.9). Among 27 treated patients with an evaluable response, 3 (11 %) achieved complete response, 5 (19 %) achieved partial response, 6 (22 %) had stable disease and 13 (48 %) patients experienced a progressive disease. The overall response rate (ORR) was 30 %, and the disease control rate (DCR) was 52 %. A quarter of all patients had at least one immune related adverse events (irAEs). Only one patient had grade 3 event, there were no grade 4 and no fatal events. Higher response rate was achieved in patients with irAE – ORR was 43 % and DCR was 71 %. Seven patients are still on cemiplimab. Conclusions: Cemiplimab has shown meaningful efficacy with DCR of 52 % in patients with laSCC and mSCC in Slovenia. Patients developing irAE had higher response rate.