Purpose Omalizumab is a monoclonal anti-IgE antibody used to treat patients with chronic spontaneous urticaria by decreasing free IgE levels. Omalizumab may have an anti-inflammatory effect by inhibiting T-cell activation and inducing eosinophil apoptosis. In this study, we evaluated the effect of omalizumab on hematological parameters and inflammation biomarkers in patients with chronic spontaneous urticaria. Methods Between July 2018 and November 2019, medical records of 60 patients (44 female, 16 male) with chronic spontaneous urticaria who were treated with omalizumab were reviewed retrospectively. Hematological parameters and inflammation biomarkers including the neutrophil/lymphocyte, monocyte/lymphocyte, platelet/lymphocyte and mean platelet volume/platelet count ratios were compared before and after 12 weeks of omalizumab treatment. Results The absolute count of basophils and percentage of basophils increased significantly after omalizumab treatment (p = 0.04, p = 0.004). The absolute count of eosinophils, percentage of eosinophils, neutrophil/lymphocyte, monocyte/lymphocyte, and mean platelet volume/platelet ratios decreased, while platelet/lymphocyte ratio increased after omalizumab treatment. Nevertheless, these changes were not statistically significant. Conclusions Increased basophil counts suggest that omalizumab has a crucial effect through basophils in chronic spontaneous urticaria. Further studies focussing on basophils may contribute to the literature both to elucidate the etiopathogenesis of urticaria and to improve novel treatment agents for the disease. On the other hand, our study revealed that omalizumab did not have a distinct effect on complete blood count-derived inflammation biomarkers and thus inflammation.