Background Acute febrile illness (AFI) is an important cause for seeking health care among children. Knowledge of the most common etiologic agents of AFI and its seasonality is limited in most tropical regions. Methodology/Principal findings To describe the viral etiology of AFI in pediatric patients ([less than or equal to]18 years) recruited through a sentinel enhanced dengue surveillance system (SEDSS) in Southern Puerto Rico, we analyzed data for patients enrolled from 2012 to May 2018. To identify seasonal patterns, we applied time-series analyses to monthly arboviral and respiratory infection case data. We calculated coherence and phase differences for paired time-series to quantify the association between each time series. A viral pathogen was found in 47% of the 14,738 patients. Influenza A virus was the most common pathogen detected (26%). The incidence of Zika and dengue virus etiologies increased with age. Arboviral infections peaked between June and September throughout the times-series. Respiratory infections have seasonal peaks occurring in the fall and winter months of each year, though patterns vary by individual respiratory pathogen. Conclusions/Significance Distinct seasonal patterns and differences in relative frequency by age groups seen in this study can guide clinical and laboratory assessment in pediatric patients with AFI in Puerto Rico.