Background: The effect of association between chronic obstructive pulmonary disease (COPD) and diabetes (DM) on platelet function has not been studied before. Objectives: To evaluate the effect of the association between COPD and DMon platelet function and C reactive protein (CRP). Patients and Methods: This case control study was carried out on 110 stable COPD patients who were classified into diabetic and nondiabetic groups. In addition, 40 apparently healthy, age and sex-matched individuals were included in this study as a control group. Chest X-ray, pulmonary function testing and arterial blood gases were done for COPD patients. CRP and complete blood count (CBC) were measured in both patient and control groups. Results: Mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and CRP were significantly higher in COPD patients either nondiabetic or diabetic compared to control group. Moreover, MPVand CRP markers were significantly higher in COPD diabetic patients compared to nondiabetic. There was no significant difference in various laboratory data among different stages of COPD either diabetic or nondiabetic (P>0.05). In COPD patients, MPV was a significantly positively correlated with CRP and PDW(r50.346, P0.001; r50.510, P0.001, respectively) and negatively correlated with PLT count (r520.294, P50.002). Conclusion: MPV, PDW, PCT and CRP were significantly higher in COPD patients either nondiabetic or diabetic. Platelet function may be modified by the systemic inflammation that associated with COPD. Platelet activation as a prothrombotic sequence of this disease may be used as novel therapeutic target. Please cite this paper as: Makhlouf HA, Sadek SH and Nafady AA. Platelet function in diabetic and nondiabetic patients with chronic obstructive pulmonary disease: a case control study. Clin Respir J 2016; 00: 000–000 DOI:10.1111/crj.12477.