The co-occurrence of COVID-19 with endemic diseases is a public health concern that may affect patient prognosis and outcomes. The objective of this study was to describe the clinical characteristics of patients with dengue virus (DENV) and SARS-CoV-2 co-infections and compare their outcomes against those of COVID-19 patients without dengue. A cross-sectional study was conducted in patients with SARS-CoV-2 infection who attended a single center in Cali, Colombia, from March 2020 to March 2021. All patients who were tested by both real-time polymerase chain reaction for SARS-CoV-2 and IgM/NS1 for DENV were included. Dengue was diagnosed as having either an IgM- or an NS1- positive test. A total of 90 patients were included (72 with COVID-19 only and 18 with co-infection). Patients with co-infection had more dyspnea (61.1% versus 22.2%; P = 0.003) as well as higher oxygen desaturation (53.3% versus 13.4%; P = 0.002) and neutrophil-to-lymphocyte ratio (5.59 versus 3.84; P = 0.038) than patients with COVID-19 alone. The proportion of patients classified with moderate to severe COVID-19 was higher in the co-infection group (88.3% versus 47.8%; P = 0.002). Also, co-infection was associated with an increased need for mechanical ventilation (P = 0.06), intensive care unit (ICU) initial management (P = 0.02), and ICU admission during hospitalization (P = 0.04) compared with COVID-19 only. The ICU mortality rate was 66.6% in patients with co-infection versus 29.4% in patients infected with only SARS-CoV-2 (P < 0.05). The possibility of DENV and SARS-CoV2 co-infection occurred in the convergence of both epidemic waves. Co-infection was associated with worse clinical outcomes and higher mortality in ICU-admitted patients than in patients with the COVID-19 only.