A field study was carried out to evaluate common practices in the study area with regard to determining the appropriate stocking density, SD for the culture of Nile tilapia, Oreochromis niloticus in a polyculture system with thin-lipped mullet, Chelon ramada, and African catfish Clarias gariepinus for 129 days. Thus, fish reared in earthen ponds (400 m³ in the volume of each) at low SD (T₁, 5.62 fish m^–3), and high SD (T₂, 11.12 fish m^–3), and assessment of their effects on productive performance, body chemical composition, physiological responses, and economic efficiency. Fish reared at low SD (T₁) attained a high (P ≤ 0.05) growth rate, the best-feed conversion ratio, improved hematological, and serum biochemical parameters, and body composition of fish compared to those reared at high SD (T₂). Fish in T₁ also achieved high fish weight categories and the best economic efficiency parameters than those reared in T₂. Thus, based on the obtained results under the cultivation conditions in the fish farm area, it could be concluded that the suitable SD is 5.62 fish m^–3 (T₁) for rearing Nile tilapia in a polyculture system with thin-lipped mullet, and African catfish in earthen ponds.