Background The aim of this study was to evaluate whether Interleukin-6 (IL-6) could be a faster indicator of treatment success in adults with severe sepsis and septic shock compared to procalcitonin (PCT) and C-reactive protein (CRP). Methods Data from adult patients with severe sepsis and septic shock managed at the medical intensive care unit (ICU) of the University Hospital Leipzig between September 2009 and January 2012 were analyzed retrospectively. Values for CRP, PCT and IL-6 on admission as well as after 24 and 48–72 h were collected. Antibiotic therapy was defined as clinically successful if the patient survived ICU stay. Results A total of 328 patients with severe sepsis and septic shock with adequate data quality were included. After 48–72 h, the median IL-6 was significantly lower in survivors than in non-survivors (114.2 pg/ml vs. 746.6 pg/ml; p < 0.001), while there was no significant difference for PCT (5.6 vs. 4.9 ng/ml; p = 0.586) and CRP (158.5 mg/l vs. 172.4 mg/l; p = 0.988). Conclusions The results of this study suggest that IL-6 is better than PCT and CRP in predicting the treatment success in predominantly non-surgical sepsis in the first 48–72 h.