Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3–stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P <.05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P <.05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.