The widespread agricultural polyphagous insect pest Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae) infests various crops especially the Egyptian cotton. Safer alternatives for insect pest control are needed due to the drawbacks of current insecticide used in agriculture settings. The neonicotinoid imidacloprid and the spinosyn biopesticide spinosad are widely used in crop systems to fight against a broad spectrum of phytophagous insect pests. Although spinosad and imidacloprid have been used in separate trials against S. littoralis, nothing is known about the impact of their binary mixing. Thus, the current research investigated the effects of imidacloprid at sublethal levels and spinosad alone and in combination on the antifeedant activity and the histomorphological changes probably caused in the midgut of S. littoralis 4^th-instar larvae. Using the leaf-dip technique approach, on castor-bean Ricinus communis leaves that had been treated, larvae were fed for three days in a row (treatment period). In case of the midgut histological study, for two days in a row, new, untreated leaves were substituted for the treated ones (recovery period). The most effective antifeedant was imidacloprid. Which was about 1.30, 1.41, and 1.29 times more than that of spinosad on the 1st, 2nd, and 3rd day post-treatment, respectively. Beside, imidacloprid was about 1.46, 1.11, and 1.18 more than that of the combined imidacloprid and spinosad on the 1st, 2nd, and 3rd day post-treatment, respectively. Compared to the midgut of untreated larvae (controls), the treated larvae's midgut displayed changes after 3 days of treatment, 1^st and 2^nd day of recovery. Muscle layer disintegration, epithelial cell disarray, peritrophic membrane separation, basement membrane detachment, and epithelium vacuolization were among the histological abnormalities. Combining spinosad and imidacloprid would reduce the amounts of each pesticide when used separately. This might result in less environmental degradation and prevent the development of resistance.