Fifty-three patients with resected pancreatic adenocarcinoma were studied to determine if adjuvant chemo-radiation causes severe lymphopenia and if this is associated with adverse outcomes. Total lymphocyte counts (TLC) were normal in 91% before adjuvant chemo-radiation. Two months later, TLC fell by 63% (p < .0001) with 45% of patients having TLC < 500 cells/mm(3). Median survival in patients with low TLC was 14 versus 20 months (p = .048). Multivariate analysis revealed a significant association between treatment related lymphopenia and survival (HR 2.2, p = .014). Adjuvant chemo-radiation induced lymphopenia is frequent, severe, and an independent predictor for survival in patients with resected pancreatic adenocarcinoma.