Background: Acute central nervous system (CNS) infections are associated with significant morbidity and mortality. Serum lactate has been shown to be a valuable prognostic marker in various infectious diseases. This study aimed to evaluate the prognostic value of serum lactate levels in predicting outcomes in patients with acute CNS infections. Methods: A cohort study was conducted, including 200 patients with acute CNS infections admitted to a tertiary care center between January 2023 and December 2023. Serum lactate levels were measured at admission, and clinical outcomes, including in-hospital mortality, length of hospital stay, ICU admission, and neurological sequelae, were assessed. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to evaluate the prognostic value of serum lactate. Results: Non-survivors had significantly higher serum lactate levels compared to survivors (median 4.2 mmol/L vs. 2.1 mmol/L, p < 0.001). The optimal cut-off value for serum lactate in predicting in-hospital mortality was 3.5 mmol/L (sensitivity 72%, specificity 80%, AUC 0.78). Serum lactate > 3.5 mmol/L (aOR 6.3, 95% CI: 2.9-13.8, p < 0.001), age > 60 years (aOR 2.7, 95% CI: 1.3-5.8, p = 0.01), and GCS score < 8 (aOR 3.9, 95% CI: 1.8-8.5, p = 0.001) were independent predictors of in-hospital mortality. Patients with serum lactate > 3.5 mmol/L had longer hospital stays (median 18 vs. 10 days, p < 0.001), higher rates of ICU admission (65% vs. 30%, p < 0.001), and worse neurological outcomes (GOS 1-3: 45% vs. 20%, p < 0.001). Conclusions: Elevated serum lactate levels at admission are significantly associated with adverse outcomes in patients with acute CNS infections. Serum lactate may serve as a valuable prognostic marker to guide risk stratification and management in this patient population.