In recent years, there have been an increasing number of studies on the Delta Neutrophil Index — DNI, C Reactive Protein – CRP and Interleukin 8 – IL8 as early markers for developing sepsis and risk of death. The study aimed to examine DNI, CRP and IL-8 in septic and non-septic patients and determine their predictive value as markers for sepsis. A prospective non-interventional single-centre clinical follow-up was performed. The study was conducted from January 2017 to July 2018 in a Bulgarian ICU in the city of Varna. DNI is a significantly critical marker for developing sepsis (Exp (B)=1.329, p= 0.007). DNI has an association with developing sepsis (r=0.363, p=0.001). ROC analysis showed a DNI value of 1.4(the best cut-off value 1.4), with 73% sensitivity and 87% specificity (AUC 0.764, 95% CI 0.650-0.878, p=0.0001). CRP is a significant marker for severity of infection and shows the likelihood of sepsis events (Exp(B)=1.016, p=0.0001). The ROC curve results demonstrate that CRP, with 82% sensitivity and 76% specificity, predict sepsis development (AUC 0.885, 95% CI 0.813-0.956, p -0.0001). There is a correlation, indicating an IL-8 increase as a marker for sepsis (r = 0.461. P = 0.0001). IL8 was significantly higher in sepsis groups than in the control group (t=3,537, р<0.001). Our results show that DNI, CRP and IL-8 are reliable indicators of high predictability for the development of sepsis, and their careful monitoring will help in the early detection of these patients and their timely treatment.