Several arboviruses have emerged or reemerged into the New World during the past several decades, causing outbreaks of significant proportion. In particular, the outbreaks of Dengue virus (DENV), Zika virus, and Chikungunya virus (CHIKV) have been explosive and unpredictable, and have led to significant adverse health effects. These viruses are considered the leading cause of acute undifferentiated febrile illnesses in Colombia. However, Venezuelan equine encephalitis virus (VEEV) is endemic in Colombia, and arboviruses such as the Mayaro virus (MAYV) and the Oropouche virus (OROV) cause febrile illnesses in neighboring countries. Yet, evidence of human exposure to MAYV and OROV in Colombia is scarce. In this study, we conducted a serosurvey study in healthy individuals from the Cauca Department in Colombia. We assessed the seroprevalence of antibodies against multiple arboviruses, including DENV serotype 2, CHIKV, VEEV, MAYV, and OROV. Based on serological analyses, we found that the overall seroprevalence for DENV serotype 2 was 30%, 1% for MAYV, 2.6% for CHIKV, 4.4% for VEEV, and 2% for OROV. This study provides evidence about the circulation of MAYV and OROV in Colombia, and suggests that they-along with VEEV and CHIKV-might be responsible for cases of acute undifferentiated febrile illnesses that remain undiagnosed in the region. The study results also highlight the need to strengthen surveillance programs to identify outbreaks caused by these and other vector-borne pathogens.