Background/Aim. Gram-positive and Gram-negative bacteria may induce different inflammatory patterns. The aim of this study was to examine the association of the myeloid-derived suppressor cells (MDSCs) with the type of infecting microorganisms (Gram positive, Gram negative, polymicrobial) and underlying cause of secondary sepsis (peritonitis, pancreatitis, trauma). Methods. Totally, 40 critically ill patients with secondary sepsis were enrolled in the prospective study. Two patients without documented positive blood culture were excluded. We detected and enumerated both main sub-sets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)-MDSCs on the Days 1 and 5. Blood was simultaneously drawn for a blood culture. The patients with different underlying causes of sepsis (peritonitis, pancreatitis, trauma) were perceived as separated groups and the frequencies and abso-lute numbers of their G-MDSCs and M-MDSCs were compared. Results. Both main MDSC subpopulations were ac-cumulated significantly in Gram-positive sepsis. Univariate logistic regression analyses of investigated variables regarding Gram-positive sepsis on the Day 5 revealed that G-MDSCs absolute number along with both M-MDSCs frequency and absolute number had statistically significant power for predicting Gram-positive sepsis. Stepwise multivariate logistic regression analyses of the variables on the Day 5 determined that M-MDSCs absolute number was independent predictor of Gram-positive sepsis [odds ratio (OR) 1.012; p < 0.05]. Clinical accuracy of neutrophil (Ne)/G-MDSCs (Ne/G-MDSCs) and monocyte (Mo)/M-MDSCs (Mo/M-MDSCs) ratios in predicting nature of bacteremia and outcome were investigated. Discriminative power of both Ne/G-MDSCs and Mo/M-MDSCs ratios in predicting Gram-positive blood culture was statistically significant both on the Day 1 and Day 5 [areas under curve (AUCs): 0.684 and 0.692, and 0.707 and 0.793, respectively). Ne/G-MDSCs both on the Day 1 and Day 5 were statistically significant predictors of lethal outcome (AUCs: 0.694 and 0.678, respectively). There were no statistically significant differences in G-MDSCs and M-MDSCs among different three groups of patients regarding peritonitis, pancreatitis and trauma as causes of sepsis neither on the Day 1 nor on the Day 5. Conclusion. Gram-positive infectious agents were powerful inducers of MDSCs generation in sep-sis. Also, underlying causes of secondary sepsis might not seem to influence the MDSCs accumulation.