Background: Prediction of complications after pancreatoduodenectomy (PD) remains of interest. Blood parameters and biomarkers during first and second postoperative days (POD1, POD2) may be early indi- cators of complications.Methods: This case-control study included 50 patients. Baseline, POD1 and POD2 values of leukocytes, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein (CRP), procalcitonin and arterial lac- tate were compared between individuals presenting Clavien ≥ III morbidity, pancreatic fistula (PF) or clinically relevant PF (CRPF) and those without these morbidities. Common variables reaching significance were further analyzed in order to calculate a predictive score. Results: Severe morbidity, PF and CRPF rates were 28.0％, 26.0％ and 14.0％, respectively. Patients with severe morbidity had lower leukocytes on POD2 ( P = 0.04). Patients with PF presented higher CRP on POD2 ( P = 0.001), higher lactate on POD1 ( P = 0.007) and POD2 ( P = 0.008), and lower lymphocytes on POD1 ( P = 0.007) and POD2 ( P = 0.008). Patients with CRPF had lower leukocytes and neutrophils on POD1 ( P = 0.048, P = 0.038), lower lymphocytes on POD1 ( P = 0.001) and POD2 ( P = 0.003), and higher CRP on POD2 ( P = 0.001). Baseline parameters and procalcitonin obtained no statistical associations. Score was defined according to lymphocytes on POD1 < 650/μL and CRP on POD2 ≥ 250 mg/L allocating patients in 3 risk categories. PF and CRPF rates were statistically higher as risk category increased ( P < 0.001). Receiver operating characteristic curves and Hosmer-Lemeshow tests showed a good accuracy. Conclusions: Impaired immunological reaction during early postoperative period (lower leukocytes and, particularly, lymphocytes) in response to surgical aggression would favor complications after PD. Likewise, acidosis (higher arterial lactate) could behave as risk factor of PF. An elevated CRP on POD2 is also an early biomarker of PF. Our novel score based on postoperative lymphocyte count and CRP seems reliable for early prediction of PF.