Background: Dengue fever (DF) is a mosquito‐borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low‐resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020.Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1–10 of fever. Participants were classified as DF‐negative and DF‐positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed‐models, we assessed if hematologic values/trajectories differed by DF status/severity.Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF‐positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001).Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk‐stratified screenings for resource‐limited settings.