We investigated the role of the lymphocyte-to-monocyte ratio (LMR) at diagnosis in patients with small cell lung cancer (SCLC) treated with standard chemotherapy. We retrospectively reviewed all SCLC patients who received frontline platinum-based chemotherapy or chemoradiotherapy. The cut-off LMR value at diagnosis was 4.19 according to time-dependent receiver-operating characteristic analysis. A total of 188 patients were divided into two groups according to the LMR at diagnosis (low vs. high LMR). Of the 171 patients evaluated for treatment response, 14 (12.4%) in the low LMR group and 1 (1.7%) in the high LMR group were non-responders (p = 0.025). In the whole patient cohort, progression-free survival and overall survival were significantly shorter in the low LMR group (low vs. high: median 6.4 vs. 7.1 months, p = 0.001; median 10.6 vs. 13.1 months, p = 0.003, respectively). On multivariate analysis, a low LMR at diagnosis was an independent unfavourable prognostic factor for predicting survival. The LMR at diagnosis could be helpful for predicting prognosis in SCLC.