BACKGROUND AND OBJECTIVES: Immune checkpoint inhibition (ICI) has revolutionized treatment for metastasized melanoma, but many patients remain unresponsive. Concerning potential adverse events, reliable biomarkers to predict ICI response are needed. In this context, neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) have emerged. Liver metastases also limit ICI efficacy, correlating with diminished overall survival (OS) and progression-free survival (PFS) and may siphon activated T cells from the systemic circulation, creating an 'immune desert state'. We evaluated the predictive role of NLR and dNLR for ICI response and the impact of liver metastases on systemic immunity and treatment efficacy. PATIENTS AND METHODS: In this single-center retrospective study, we included 141 stage IV melanoma patients undergoing ICI. NLR and dNLR were calculated from absolute neutrophil count, absolute lymphocyte count, and white blood cell count. RESULTS: Elevated NLR and dNLR were associated with poor response to ICI and inferior PFS. Patients with liver metastases exhibited higher NLR and dNLR levels and showed diminished response to ICI. CONCLUSIONS: Elevated baseline NLR and dNLR predict poor response to ICI and PFS in stage IV melanoma. Liver metastases are negative predictors for ICI response, with associated higher NLR and dNLR levels potentially contributing to therapy resistance.