Background <p>Severe dengue has been linked to the presence of atypical lymphocytes, which can be quantified using the Q-flag parameter on a hematology analyzer. A higher atypical lymphocyte count has previously been associated with severe dengue. We aimed to evaluate the feasibility of the atypical lymphocyte score to provide an early prognosis for dengue severity.</p> Method <p>A prospective observational study enrolled adult patients admitted to the Infectious Disease ward with a febrile illness of less than 7 days. Blood samples obtained daily until discharge, were processed with XN-20 hematology analyzer with specific attention given to atypical lymphocyte score. Severe dengue cases were classified according to the 2009 World Health Organization Classification.</p> Results <p>A total of 287 cases of laboratory-confirmed dengue, including 25 severe cases, were included. Dengue fever compared to non-dengue patients manifested increased lymphocytes within the high fluorescent zone on Day 6,</p> <p>The atypical lymphocyte score (ALS) of severe dengue showed an early rise, reaching a saturation point of 300 and remaining stable within the timeframe of days 4 to 8 post-fever onset. All but one severe dengue patient had a score exceeding 100 on day 4 post fever onset.</p> Conclusion <p>An atypical lymphocyte score below 100 on day 4 post fever onset, may serve as a predictive indicator that severe dengue is less likely to develop, potentially allowing for a lower level of medical intervention. These findings may contribute to more efficient resource allocation during outbreaks.</p> Trial registration <p>The study was registered under National Medical Research Registration of Malaysia, (NMRR-18–3347-45473, 1 Sept 2019).</p>