The response of the cotton leafworm, Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae), to lethal, sublethal and biochemical parameters effects of clothianidin and metaflumizonewere determined by a leaf dipping technique bioassays. Mortality of newly molted 4^th instar larvae increased with the concentration resulting LC₅₀ values of 70.24 ppm and 20.41 ppm, for clothiandin and metaflumizone respectively. Sublethal effects were studied by treatment of 4^th instar larvae with a concentration equivalent to LC_50. The larval development time, from treatment until pupation, of the survivors were significantly increased in both insecticides, the pupation period shorted significantly for both sex but shorted insignificantly in male pupa treated with clothianidin, and the weighty of pupa was reduced significantly in both insecticides. However, no significant differences were found in the oviposition and oviposition days viability and percentage of egg viability, but significant differences were found in the preoviposition days when larvae treated with metaflumizone, fecundity percentage decreased in both insecticides and adult longevity was shorted in either both sex or both insecticides. Biochemical analysis indicated that while treatment of 4th instar larvae with LC50 of both pesticides had no significant effect on acetylcholine esterase activity (AChE) in larval homogenate, it significantly decreased larval contents of total protein and total carbohydrates, reduced alkaline phosphatase (ALP), and esterase (EST) activities, and increased glutathione-s-transferase (GST) acitivity.