The Egyptian cotton leafworm is considered the major pest that causes great damage to cotton plants as well as other vegetable crops in Egypt. This study was planned to evaluate the efficacy of emamectin benzoate, indoxacarb and lufenuron compounds against the cotton leafworm, Spodoptera littoralis and its natural predator Coccinella spp. during the two successive seasons of 2017 and 2018. The obtained results indicated that lufenuron compound was the most against the cotton leafworm followed by emamectin benzoate during the two experimental seasons; while the indoxacarb was the lowest toxic on Coccinella spp. Conclusively, it could be recommended to use lufenuron and indoxacarb insecticides to control the cotton leafworm in cotton fields with relatively low effect on natural predator.