A 14-week trial was undertaken to examine the effects of coenzyme Q10 (CQ10) and l-carnitine (LC) dietary supplementation, either individually or in combination, on the feed intake, growth, blood biochemistry, immunity, economic viability, and body composition of Nile tilapia fingerlings reared at a high stocking density. The study involved eight groups of 450 tilapia juveniles, with an average weight of 6.083 ± 0.09 g, assigned to different treatments. Two groups were fed a basal diet and stocked at densities of 30 and 60 fish per m3, respectively. The remaining groups were reared at a high stocking density of 60 fish/ m3 and fed diets fortified with LC at 150 mg (G3), LC at 300 mg (G4), CQ10 at 20 mg (G5), CQ10 at 40 mg (G6), LC at 150 mg + CQ10 at 20 mg (G7), or LC at 300 mg + CQ10 at 40 mg (G8) per kg of diet. The findings revealed that high stocking density had an adverse impact on tilapia growth performance. Nevertheless, the inclusion of LC and CQ10 in the diet, whether separately or in combination, significantly improved growth parameters and enhanced survival rates. The G6, G7, and G8 groups showed the most significant improvements in growth and survival. High stocking density resulted in decreased moisture and crude protein content, while LC and CQ10 supplementation increased these components and reduced crude fat and ash content. High stocking density negatively impacted blood metabolites, leading to elevated levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and urea-N, as well as decreased total protein and albumin. However, supplementation with LC and CQ10 effectively alleviated these effects, improving the levels of these parameters. All supplemented groups showed enhanced lysozyme activity and IgM concentration, with the greatest improvements observed in the G6, G7, and G8 groups. Economic analysis indicated that LC and CQ10 supplementation improved final and relative margin, except in the G4 group. In conclusion, the combined supplementation of LC and CQ10 shows promise in enhancing productivity and profitability in tilapia farming under high stocking density conditions, particularly in concrete tanks.