Immunotherapy provides new hope to individuals with small cell lung cancer (SCLC). Predicting biomarkers for clinical effects is crucial for SCLC patients receiving programed death-ligand 1 (PD-L1) inhibitor treatment. The aim of this study was to clarify the value of serum lipids as predictors of immune related adverse events (irAEs) and the anti-tumour effects in SCLC patients who received PD-L1 inhibitors as first-line treatment. This study included patients with SCLC who received at least one cycle of PD-L1inhibitors at Shanghai Pulmonary Hospital from August 2020 to December 2023. We collected the clinical data of the SCLC patients, including basic information and serum lipid levels, before immunotherapy. The irAEs rate was 16.1% of 124 enrolled patients. In multivariate analysis, the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was an independent predictor of irAEs (p = 0.045). Tumour response analysis indicated that the objective response rate (ORR) was 43.4% and the disease control rate (DCR) was 79.5%. Seventy-seven patients experienced any progression-free survival (PFS) event. The median PFS was longer in the HDL-C-high group (10.03months) than in the HDL-C-low group (6.67months) (p = 0.043). In Cox regression analysis, the serum HDL-C level was an independent predictor of PFS (p = 0.002). For patients of the high TG/HDL-C ratio, the ORR significantly differed between patients who suffered from any irAEs and those who did not (p = 0.0139). This study found that serum lipid levels might predict the responses to anti-PD-L1 as first-line treatment for SCLC.