Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) with high density lipoprotein (HDL) cholesterol levels in coronary artery disease (CAD) patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P = 0.008) and NLR (P = 0.009); however no significant relationship was obtained with HDL and isolated platelet (P = 0.488), neutrophil (P = 0.407), and lymphocyte (P = 0.952) counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P = 0.024) and NLR (P = 0.03) were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P = 0.01) and NLR (6.33 versus 5.10; P = 0.01) were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P = 0.007) and NLR (P = 0.001) were inversely associated with HDL, whereas in older population only NLR (P = 0.05) had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.