Seaweeds have gained focus as a sustainable aquafeed ingredient due to their restricted land-based resources requirement and their highest nutritional value. The present study was designed to investigate the effect of a partial replacement of soybean meal (SBM) with dried seaweeds Ulva lactuca meal (ULM) on growth performance, feed efficiency, body composition, and physiological responses of the monosex Nile tilapia (Oreochromis niloticus) fry for 84 days. A total of 150 O. niloticus fry individuals, with average initial body weight (0.81± 0.02g), were randomly distributed into 5 treatments with triplicate groups in 15 glass aquaria. Five isonitrogenous (30% crude protein) and isocaloric (440 kcal/100 g) diets were formulated to contain ULM as SBM replacers at levels 0.0 (as a control diet, D₁), 5.0 (D₂), 15.0 (D₃), 25.0 (D₄) and 35.0% (D₅) substitution. The fish fed different levels of ULM, especially level 15% (D₃), showed an improvement in the rearing water quality parameters, and significantly increased growth performance, condition factor, and feed utilization, besides a recorded improvement in the hepatosomatic index, and physiological responses of O. niloticus compared to those fed the control diet (D₁). In addition, the negative effects of high levels of dietary ULM were detected on the aforementioned parameters. Thus, it could be concluded that the beneficial use of ULM instead of SBM in O. niloticus fry diet, without reaching 15%, may have an economic efficiency and environmentally friendly effects on fish farms.