Background: The recent re-emergence of dengue in the Americas region and the current COVID-19 pandemic have created a challenge for health services. Similar symptoms can be found between them especially during the first week of the disease. The objective of this study was to compare symptoms and laboratory tests of both diseases during patients' admission to the emergency rooms. Methods: A cross-sectional study was performed between March and April 2020 in Cali, Colombia. We included patients with a diagnosis of dengue and COVID-19 with age older than 15 years. All COVID-19 patients had less than 10 days of symptoms. All dengue patients had positive NS1 or positive IgM, and all dengue patients have confirmed seroconversion. A descriptive analysis was performed. A p-value <0.05 was considered statistically significant for all analyses. Findings: A total of 43 patients were included, 32 with dengue and 11 with COVID-19. There were significant differences between dengue and COVID-19 patients regarding age (median age 19.5 yr. vs. 44 yr.; p=0.001), history of fever (97% vs 27.3%; p<0.001), platelet count (88,500 vs 193,000 cell/µL; p=0.01), absolute neutrophils count (2,090 vs 4,730 cells/µL; p=0.0008), neutrophils-lymphocytes ratio - NLR (1.36 vs 3.06; p=0.037), and abnormal alanine transaminase ALT (116 vs. 37 IU per liter; p=0,007). Interpretation: During the first week of symptoms, absolute neutrophil count, NLR, and platelet count could help guide the initial differential approach between dengue and COVID-19. Dengue patients tend to be younger at admission to emergency rooms.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: This study was approved by the Institutional Review Board – Comité de Ética en Investigación Biomédica at Fundación Valle del Lili (IRB/EC No. 919) and was conducted following the Declaration of Helsinki. Patient consent was not required because this study was performed retrospectively.