Dengue is a mosquito-borne virus infection affecting half of the world’s population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progressdevelop to severe dengue (SD) from those who do not. These signatures are exacerbated in In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity potential compared to non-SD. Using transcriptional and proteomics approaches we demonstrate decreased Furthermore, type-I Interferon signalling is downregulatedresponses in SD, suggesting defective innate immunity virus-sensing mechanisms may underlie NK/T-cell dysfunction.