BACKGROUND: Cerebral gunshot wounds (CGSWs) represent a highly lethal form of traumatic brain injury, and triaging these patients is difficult. The prognostic significance of the serum lactate level in the setting of CGSWs is largely unknown. OBJECTIVES: To examine the relationship between elevated serum lactate levels and mortality in patients with isolated CGSWs. METHODS: A retrospective review of the regional trauma registry was undertaken at the Pietermaritzburg Metropolitan Trauma Service, South Africa, over a 5-year period from 1 January 2010 to 31 December 2014. All patients with an isolated CGSW were included. RESULTS: A total of 102 patients with isolated CGSWs were identified. Of these, 92.2% (94/102) were male. The mean age (standard deviation) was 29 (8) years, and the in-hospital mortality rate was 21.6% (22/102). The mean serum lactate level was significantly higher among non-survivors than among survivors (6.1 mmol/L v. 1.3 mmol/L; p<0.001). Lactate levels among non-survivors were <2 mmol/L in 4.5%, 2 - 3.99 mmol/L in 9.1%, 4 - 5.99 mmol/L in 36.4% and ≥6 mmol/L in 50.0%. The odds ratio for mortality with a lactate level of 4 - 5.99 mmol/L was 67 (95% confidence interval (CI) 1.7 - 2 674.2), while for a lactate level of ≥6 mmol/L it was 1 787 (95% CI 9.0 - 354 116.1). The serum lactate level accurately predicted mortality even after adjustment for other variables. Based on a receiver operating curve analysis, an optimal cut-off of 3.3 mmol/L for serum lactate as a predictor for mortality was identified (area under the curve = 0.957). CONCLUSIONS: CGSWs are associated with significant mortality, and a raised serum lactate level appears to be an independent predictor of in-hospital mortality. It is a potentially useful adjunct in the resuscitation room for identifying patients with a very poor prognosis.