Background: Insecticide-resistant Culex quinquefasciatus mosquitoes have been reported worldwide but the susceptibility status of Cx.quinquefasciatus larvae to insecticides has not been determined in Jakarta, Indonesia. This study aimed to evaluate the susceptibility status of Cx. quinquefasciatus larvae to temephos, malathion, cypermethrin, and deltamethrin in Jakarta, Indonesia, through the mode of action detoxification enzyme activity and digestive system damage.Methods: Cx. quinquefasciatus larvae were collected from five sites in Jakarta. The larval susceptibility test to temephos used the WHO standard kits (1.25, 6.25, 31.25, and 156.25 ppm) and to malathion (0.5 ppm), cypermethrin (.25 ppm), and deltamethrin (0.35 ppm). The activity of acetylcholinesterase (AChE), glutathione S-transferase (GST), and oxidase were measured by the biochemical method. The larval midgut cell damage was examined using the routine histopathological method and transmission electron microscopy (TEM).Results: At 24 h, temephos and deltamethrin caused 100% larval death of Cx.quinquefasciatus in five sites of Jakarta. Temephos and malathion significantly inhibited AChE activity, while cypermethrin and deltamethrin significantly inhibited oxidase activity. All tested insecticides significantly damaged the larval midgut. The TEM findings showed the damaged parts of the midgut epithelial cells included the cell membrane, nuclei, nucleoli, mitochondria, and other organelles cells.Conclusion: This study is the first to report that Cx.quinquefasciatus larvae in Jakarta were completely susceptible to temephos and deltamethrin through metabolic enzymes and midgut cell damage. This study provides baseline data to improve mosquito control programs.