BACKGROUND This study aimed to evaluate the possible associations of heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP) levels with 28-day mortality in septic shock patients admitted to Intensive Care Units (ICUs). MATERIAL AND METHODS Blood samples were taken at ICU admission and measured again 72 h later to calculate changes in HBP (ΔHBP), changes in PCT (ΔPCT), changes in CRP (ΔCRP), and changes in Sequential Organ Failure Assessment (DSOFA) relative to baseline. RESULTS Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, decreasing ΔSOFA, decreasing DHBP, decreasing ΔPCT, and decreasing ΔCRP. Survival was directly related to decreasing ΔHBP with odds ratio (OR)=9.95 (95% confidence interval [CI] 4.63 to 21.35; P<0.001), decreasing ΔPCT with OR=7.85 (3.74 to 16.49; P<0.001), decreasing ΔCRP with OR=5.83 (2.84 to 11.97; P<0.001), decreasing ΔSOFA with OR=1.93 (1.00 to 3.75; P=0.051) and APACHE II score with OR=1.93 (1.14 to 1.68; P=0.001). In a multivariable logistic regression model for survival, only decreasing DHBP with OR=7.18 (2.91 to 17.69; P<0.001), decreasing ΔPCT with OR=5.17 (2.12 to 12.56; P<0.001), and decreasing ΔCRP with OR=4.33 (1.77 to 10.61; P=0.001) remained significant. CONCLUSIONS Measuring changes in HBP, PCT, and CRP within 72 h of admission may aid in predicting 28-day mortality for patients with septic shock in ICUs.