Cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae) is considered a key pest of cotton in Egypt. Hence, field and laboratory studies were conducted at Sakha Agriculture Research Station, Egypt during seasons 2016 and 2017. Efficiency of seven insecticides i.e., flonicamid, imidacloprid, thiamethoxam, emamectin-benzoate, chlorpyrifos, methomyl and deltamethrin against A. gossypii in cotton fields were evaluated. Their side effects on the associated predators, soil fauna and plant defense enzymes also were studied. Flonicamid was the most effective against A. gossypii. The efficacy of imidacloprid and thiamethoxam did not differ significantly from that of chlorpyrifos and methomyl recording from 83.28 – 93.27% reduction in A. gossypii infestation. Flonicamid, emamectin-benzoate, imidacloprid and thiamethoxam were the least harmful to the associated predators causing less than 50% mortality, while the others were highly toxic. Flonicamid exhibited the highest degree of safety to the soil micro-arthropods, followed by emamectin-benzoate, methomyl and deltamethrin. In contrast, chlorpyrifos and imidacloprid were the most toxic to the soil micro-arthropods. The conventional insecticides (chlorpyrifos, methomyl and deltamethrin) increased the activity of catalase and peroxidase causing physiological stress on the treated cotton plants, whereas the other tested insecticides recorded decreases in catalase and peroxidase activities inducing the plant defense response. Only imidacloprid and thiamethoxam increased the activity of polyphenol oxidase. Emamectin-benzoate and deltamethrin decreased the total soluble protein content, while the others tested insecticides caused increases in this criterion comparing to the control.