Statins may exert pleiotropic effects in coronary artery disease (CAD), diabetes mellitus, and familial hypercholesterolemia. We evaluated the effects of statins on the neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) in 261 consecutive patients with hypercholesterolemia having CAD or at high cardiovascular (CV) risk and 50 healthy participants who were retrospectively included in this study. Patients were treated with 10 to 80 mg atorvastatin or 10 to 40 mg rosuvastatin for 24 weeks according to baseline levels of cholesterol, triglycerides, and CV risk. Baseline NLR and MPV were significantly higher in patients with CAD or at high risk compared to the control group (1.89 [0.37–6.78]) vs 1.44 [0.75–2.41], P < .001 and 8.8 [6.27–18.6] vs 8.45 [6–11] fL, P = .038, respectively). The NLR, MPV, and lipid parameters were also compared in the patient group after statin treatment for 24 weeks. Lipid levels decreased but the NLR and MPV did not change significantly after the statin therapy. Further studies are needed to clarify the effect of statin therapy on NLR and MPV in patients with CAD or at high CV risk.