The role of neutrophil and lymphocyte counts in blood as prognosis predictors in Community Acquired Pneumonia (CAP) has not been adequately studied. This was a derivation-validation retrospective study in hospitalized patients with CAP and no prior immunosuppression. We evaluated by multivariate analysis the association between neutrophil and lymphocyte counts and mortality risk at 30-days post hospital admission in these patients. The derivation cohort (n = 1550 patients) was recruited in a multi-site study. The validation cohort (n = 2846 patients) was recruited in a single-site study. In the derivation cohort, a sub-group of lymphopenic patients, those with < 724 lymphocytes/mm3, showed a 1.93-fold increment in the risk of mortality, independently of the CURB-65 score, critical illness, and receiving an appropriate antibiotic treatment. In the validation cohort, patients with < 724 lymphocytes/mm3 showed a 1.86-fold increment in the risk of mortality. The addition of 1 point to the CURB-65 score in those patients with < 724 lymphocytes/mm3 improved the performance of this score to identify non-survivors in both cohorts. In conclusion, lymphopenic CAP constitutes a particular immunological phenotype of the disease which is associated with an increased risk of mortality. Assessing lymphocyte counts could contribute to personalized clinical management in CAP.