Dengue, caused by the dengue virus (DENV), poses a significant global health challenge. Effective vaccines and treatments for dengue are lacking due to gaps in understanding its pathogenesis and mechanisms in severe cases. This study investigates the role of immunoglobulin E (IgE) in dengue, focusing on its potential association with virus neutralization and antibody-dependent enhancement (ADE) in DENV replication. Serum samples were obtained from dengue-positive (dengue-IgG positive), SLE (dengue-IgG negative), and control (dengue-IgG and SLE-negative) individuals. SLE sera were included as a control for their high total IgE levels. Total IgE and dengue-specific IgE levels were measured using ELISA. Neutralization assays in Vero and KU812 cells were conducted to assess virus neutralization and ADE, respectively. Dengue-positive and SLE sera showed higher total IgE levels than control sera, although there was no significance seen. Dengue-positive sera showed the presence of dengue-specific IgE, whereas SLE and control sera exhibited negligible levels. Neutralization assay in dengue-positive sera revealed no correlation between IgE levels and virus inhibition. SLE sera, however, demonstrated an inverse correlation between total IgE levels and DENV neutralization, suggesting a potential involvement of total IgE in DENV replication in the context of SLE. Seventy-eight percent of SLE sera, 65% of denguepositive and 54% of control sera exhibited enhanced virus replication in KU812 cells with serum compared to virus alone, indicating the highest occurrence of ADE in SLE, followed by dengue-positive and control sera. DENV expression in KU812 cells was notably higher in SLE sera, indicating increased ADE risk. However, no association was found between IgE levels and virus expression in KU812 cells across all groups. The inverse correlation between total IgE levels and DENV neutralization in SLE sera suggests that IgE may facilitate virus replication. Further comprehensive exploration is needed to fully understand the role of IgE in dengue pathogenesis.