(1) Background: Recent research suggests inflammation as a factor involved in the pathophysiology of mood disorders. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and systemic immune-inflammatory (SII) index ratios have been studied as peripheral markers of inflammation in bipolar and major depressive disorders. The purpose of this study is to comparatively analyze these inflammatory ratios among manic episodes of bipolar disorder, bipolar depression and unipolar depression. (2) Methods: 182 patients were retrospectively included in the study and divided into three groups: 65 manic patients, 34 patients with bipolar depression, and 83 unipolar depressive patients. White blood cells, neutrophils, monocytes, lymphocytes, and platelets were retrieved from the patients' database. NLR, MLR, PLR, and SII index were calculated using these parameters. (3) Results: Patients with manic episodes had elevated NLR ( < 0.001), MLR ( < 0.01), PLR ( < 0.05), and SII index ( < 0.001) compared to unipolar depression and increased NLR ( < 0.05) and SII index ( < 0.05) when compared to bipolar depression. NLR ( < 0.01) and SII index ( < 0.05) were higher in the bipolar depression than unipolar depression. NLR is an independent predictor of the bipolar type of depression in depressive patients. (4) Conclusions: The results confirm the role of inflammation in the pathophysiology of mood disorders and suggest the ability of NLR as a marker for the differentiation of bipolar from unipolar depression.