The aims of this study were to investigate a clinical observation that patients with epithelial ovarian cancer treated with first-line platinum–paclitaxel chemotherapy combination (TP) develop macrocytosis and to explore the possible predictive role of macrocytosis in response rate, progression-free survival (PFS), and overall survival. A retrospective analysis of laboratory and clinical data on 184 consecutive ovarian cancer patients treated with first-line TP chemotherapy in a single oncology center from 2004 to 2015 was carried out. Macrocytosis was defined as an increase in mean corpuscular volume of peripheral red blood cells above 97.2 fl during the treatment and/or 30 days after the last chemotherapy cycle. One hundred and forty-one patients were treated with a conventional 3-weekly TP schedule, whereas 43 patients were treated with a dose-dense schedule. Macrocytosis was induced in 35% of patients overall. It was induced significantly more often in patients treated with the dose-dense schedule than in those treated with the 3-weekly schedule (67 vs. 26%, P=1.29×10−6). Macrocytosis did not correlate with PFS and overall survival in the overall patient population, nor in patients treated with the 3-weekly schedule. It correlated with PFS (hazard ratio=0.42, 95% confidence interval=0.18–0.94, P=0.036) and objective response on therapy in patients treated with the dose-dense schedule (P=0.0285). Dose-dense TP chemotherapy induces macrocytosis significantly more often than does a 3-weekly schedule in ovarian cancer patients. In patients treated with a dose-dense schedule, macrocytosis can potentially be predictive for longer PFS and better response rate. This finding needs further confirmation, preferentially in a prospective study.