Purpose Secondary peritonitis is still one of the most important causes of severe sepsis in the world; therefore, it is of utmost importance to identify biomarkersthat could be employed for the purpose of selecting patients at high risk for developing life-threatening complications after emergency surgery. In view of this quest, our study seeks to reveal the possible role for serum and peritoneal concentrations of selected biomarkers, specifically presepsin, procalcitonin, monocyte chemoattractant protein-1 (MCP-1), high mobility group box 1 protein (HMGB-1) and interleukins (IL-6, -8, -10), in early prediction of sepsis and septic multiorgan failure for patients with secondary peritonitis. Methods We prospectively observed 32 selected patients with secondary peritonitis that underwent emergency surgery. Blood and peritoneal fluid samples were drawn at the time of surgery (T0), and after that, blood samples were taken at 24 (T1) and 48 (T2) hours postoperatively. Cytokines concentrations were determined using a sandwich enzyme-linked immunosorbent assay (ELISA), a non-competitive variant, both in peritoneal fluid and serum. For determining whole blood concentration of presepsin and procalcitonin, PATHFAST™ assays (Polymedco, Cortlandt, New York) were used, based on the principle of non-competitive chemiluminescent enzyme immune-assay (CLEIA). The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of University Emergency Hospital Bucharest (no. 40325/6 April 2023). Results We found significant elevations in the peritoneal concentrations of interleukins 6, 8, 10, HMGB-1, and MCP-1 in all patients with secondary peritonitis at the moment of surgery; however, no clear correlation could be made based on this data with patient evolution. With regards to blood concentrations of the aforementioned serum cytokines and presepsin, procalcitonin (as already established markers of sepsis), our results showed good predictive value of presepsin for developing sepsis and septic multiorgan failure from the first hoursin this patient category. All other biomarkers, despite having higher concentrations than baseline, in particular at 24-48 hours after surgery, had unpredictable dynamics that couldn't be correlated with the severity of the disease. Conclusion Cytokine production is the mainstay in developing sepsis and septic multiorgan failure in patients with secondary peritonitis; therefore, studying the dynamics of said cytokines seems of interest in finding tools to predict the development of sepsis or sepsis-related mortality. However, at the time, there seemed to be no clear correlation between the values of these cytokines and the development of complications.