Acute Febrile illnesses are caused by diverse microbial pathogens and are associated with significant morbidity and mortality. The methodical evaluation of area-specific etiologies of AFI helps in the rapid diagnosis, treatment and prevention and control strategies. To investigate the causes of AFI, their clinical spectrum and the seasonal trend through the year. A facility based prospective study was conducted in a tertiary care hospital in Kolar, Karnataka, South India; between January 2016 to December 2016. A total of 432 patients with AFI were enrolled and screened for specific etiological agents. The etiological agents were identified in 351 (81.25%) of AFI cases. The etiological agent could not be established in 81(18.75%) of cases. Dengue was the most common cause of AFI (52.1%) followed by Scrub typhus (9.02%), Leptospirosis (6.48%), Chikungunya (5.32 %), Enteric fever (4.16%), Malaria (3.93%) and Brucellosis (0.23%). The most common symptoms reported by enrolled patients included headache (93.1%), malaise (89.4%), joint pain (80%), chills (73.7%). In our study, AFI occurred most commonly during rainy and autumn seasons accounting for 272 (77.5%) cases. Laboratory based syndromic data of AFI can make clinicians vigilant regarding the potential pathogens in local area and further aid to establish the epidemiologic database of different etiologies.