Background and purpose: Chemotherapy-induced neutropenia and neutrophil-to-lymphocyte ratio (NLR) are potentially useful prognostic markers in patients with metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis investigated whether these markers can be utilized for dose considerations and evaluated the prognostic impact of leukocyte subtypes. Patients and methods: PROSELICA assessed the non-inferiority of cabazitaxel 20 mg/m2 (C20; n = 598) versus 25 mg/m2 (C25; n = 602) for overall survival (OS) in patients with mCRPC previously treated with docetaxel. The association of grade ⩾ 3 neutropenia, NLR, baseline neutrophilia and lymphopenia with OS, progression-free survival (PFS), and prostate-specific antigen response rate (PSArr) was investigated by an unplanned uni- and multivariate analyses. Results: PROSELICA confirmed the negative prognostic value of increased baseline NLR ⩾3, hazard ratio (HR) 1.40; p < 0.0001, but did not identify a subgroup of patients benefiting more from C20 or C25. In this post hoc analysis, patients who developed grade ⩾3 neutropenia (n = 673) had a significantly improved OS ∆OS = 2.7 months, HR = 0.78 (95% CI 0.68–0.89) with the greatest advantage observed in patients with baseline neutrophilia n = 85; 5.3 months, 0.60 (0.42–0.84). After adjustment for the Halabi criteria, neutropenia grade ⩾ 3 was the only biomarker that remained significantly associated with OS (HR 0.86 (0.75–0.98), PFS HR 0.78 (0.68–0.88), and PSArr odds ratio (OR) 1.82 (1.37–2.41) while neutrophilia showed the strongest association with OS 1.53 (1.29–1.81). Conclusions: Grade ⩾ 3 neutropenia was the only leukocyte-based biomarker associated with all key outcome parameters in mCRPC patients receiving cabazitaxel and might be able to overcome the negative prognostic effect of baseline neutrophilia. NCT number: NCT01308580