Anemia, mean corpuscular volume and red cell distribution width may have some effects on survival outcomes of metastatic renal cell carcinoma (mRCC) patients and are incorporated in a red blood cell (RBC)-based score. Its validity in prognostication of mRCC patients treated with second-line nivolumab was assessed. Retrospective analysis using Meet-URO-15 cohort of mRCC patients receiving nivolumab in the second-line setting or beyond. Outcomes were overall survival (OS) and progression-free survival (PFS). A total of 390 patients were included. Significant differences in OS and PFS between RBC-based score groups, with group 1 (2 or 3 of the RBC-related prognostic factors) having longer OS (median 29.5 months, 95% CI: 23.1-35.9, versus 11.5 months, 95% CI: 8.5-22.6;  < 0.001) and PFS (7.5 months, 95% CI: 5.5-10.2, versus 4.2 months, 95% CI: 3.3-5.9;  = 0.040) than those in group 0 (0 or 1 RBC-related prognostic factors). Belonging to group 1 independently predicted OS (hazard ratio: 0.65, 95% CI: 0.50-0.85;  = 0.002) but not PFS (hazard ratio: 0.89, 95% CI: 0.70-1.14,  = 0.370) or disease response (OR 0.68, 95% CI: 0.41-1.10;  = 0.118) at multivariable analysis. RBC-based group scores independently predicted OS in mRCC patients treated with nivolumab.