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Insecticide resistance is one of the major impediments threatening the control of malaria vector populations in Nigeria. The failure of WHO recommended control, especially with permethrin used for insecticide treated nets (ITNs) and indoor spray could lead to increase morbidities and mortalities, if left unattended to. This calls for sound management approach achievable through adequate knowledge of spread and mechanism of resistance. Hence, this study evaluated resistance status and involvement of metabolic resistance in Anopheles coluzzii populations from Delta State to permethrin. Anopheline larvae were collected from three Local Government Areas (LGA) and reared to adult stage at Entomology Laboratory, Delta State University, Abraka. Adult female mosquitoes aged 3 – 5 days were exposed to 0.75% permethrin using WHO bioassay method. Also, cohort were exposed to PBO and further exposed to permethrin. Exposed mosquitoes were identified molecularly. All identified mosquitoes were An. coluzzii. Exposure of An. coluzzii populations from Ika South, Ndokwa East and Ethiope West Local Government Area to permethrin recorded 62, 74 and 83 % mortality respectively. Mortalities in synergist assay were 99, 99 and 100 % respectively. Differences in mortality between permethrin and PBO/permethrin-exposed population were significant (p<0.0001). Knockdown Time (KDT50 and KDT95) was lowest in Ethiope West LGA. Considering increase in mortality value of the populations with exposure to PBO, this study presents evidence for involvement of cytochrome P450 in development of resistance in permethrin-resistant Anopheles populations from Delta State.