Influenza virus is a common agent of acute respiratoty infections during epidemic periods. It is a major cause of morbidity and mortality and represent a significant burden on the healthcare system. We aimed to evaluate predictors of severity and of in-hospital mortality in patients hospitalized with influenza infection. We performed a retrospective cohort study of hospitalized, laboratory confirmed cases of influenza disease in Centro Hospitalar de São João between October 2016-May 2017 and October 2017-May 2018. The endpoints being analysed were severity and in-hospital mortality. A multivariate logistic regression analysis was used to determine independent predictors of severity and of in-hospital mortality. We studied 221 hospitalized influenza infection cases. Mean age 66±16 years, 57.9% were male, thirty-seven patients (16.7%) died in-hospital and 101 patients (45.7%) met severity criteria. C-reactive protein (CRP) was the only independent predictor of severity as well as the only independent predictor of higher in-hospital mortality in patients admitted due to influenza infection. Multivariate-adjusted CRP OR for severity was 1.10, 95% CI 1.06-1.15 per each 10 mg/L increase in CPR and for in-hospital mortality risk the OR was of 1.05, 95% CI 1.01-1.09, p=0.01, per each 10 mg/L increase. Concluding, in patients' hospital-admitted due to influenza infection CRP was the only predictor of severity with a 10% increased risk of inotropic support/ventilatory support/prolonged hospitalization needs and a 5% increase risk of in-hospital death per each 10 mg/l increase.