Background Sepsis is a medical emergency and necessitates immediate diagnosis and treatment to prevent the progression to severe sepsis, septic shock, and potentially mortality. Aim This study aims to study the diagnostic significance of conventional and new markers, interleukin-10 (IL-10), in predicting the severity of sepsis. Methodology A prospective observational study was conducted in the department of surgery in a tertiary care hospital in Pune, India. The study included 100 patients diagnosed with a quick Sequential Organ Failure Assessment (qSOFA) score of ≥2. Serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) levels were measured. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic performance of these biomarkers. Results The mean serum CRP level on day 7 was significantly higher than the baseline, day 1, and day 3 groups (p=0.0001). On analysis by repeated measure, the ANOVA test revealed that the mean CRP levels on day 7were significantly higher. The mean PCT levels on day 7, day 3, and day 1 groups were significantly lower than those on day 1, day 2, and day 2, respectively (p=0.0001). The mean p-value of 3.3 g/L CRP was significantly lower on day 1 than that on day 3. IL-10 levels showed a significant upward trend, rising from 5.21 pg/mL at baseline to 7.57 pg/mL by day 7, with a p-value of <0.0001. Our cohort population showed elevated IL-10 values on the day of admission in a total of 15 patients. In our study, we observed that 11 patients with elevated IL-10 levels progressed towardmultiple organ dysfunction syndrome (MODS) and four mortalities. IL-10 is a crucial marker for identifying patients with worsening surgical sepsis. Conclusion IL-10, CRP, and PCT have potential as prognostic markers in assessing and predicting disease severity.The dynamic changes in these biomarkers correlate strongly with clinical outcomes, suggesting their role in guiding treatment decisions.