Mosaic loss of Y chromosome (mLOY) is the most frequently detected somatic copy number alteration in leukocytes of men. In this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotyping arrays, and blood cell counts were assessed by multivariable linear models adjusted for relevant risk factors. Among the participants, mLOY was detected in 39,809 men. We observed associations between mLOY and reduced erythrocyte count (-0.009 [-0.014, -0.005] × 10 cells/L, p = 2.75 × 10) and elevated thrombocyte count (5.523 [4.862, 6.183] × 10 cells/L, p = 2.32 × 10) and leukocyte count (0.218 [0.198, 0.239] × 10 cells/L, p = 9.22 × 10), particularly for neutrophil count (0.174 × [0.158, 0.190]10 cells/L, p = 1.24 × 10) and monocyte count (0.021 [0.018 to 0.024] × 10 cells/L, p = 6.93 × 10), but lymphocyte count was less consistent (0.016 [0.007, 0.025] × 10 cells/L, p = 8.52 × 10). Stratified analyses indicate these associations are independent of the effects of aging and smoking. Our findings provide population-based evidence for associations between mLOY and blood cell counts that should stimulate investigation of the underlying biological mechanisms linking mLOY to cancer and chronic disease risk.