An in ovo study on the effect of the administration of a combination of nucleosides (25, 50, and 100 mg/egg) on hatchability, growth performance, energy metabolizability, and intestinal morphology in broilers was carried out. Four hundred eighty (480) fertile eggs were divided into four groups (in four replicates each having 30 eggs). On the 18th days of incubation of the eggs, candling was carried out and the fertile eggs were selected and given one of the four in ovo administrations. Group one served as control and was injected with phosphate-buffered saline (PBS). The other groups were given in ovo administration of nucleosides (25, 50, and 100 mg/egg) at 100 μl through the yolk sac route, and chicks of respective groups were hatched out. Among the experimental groups, the hatchability was comparable; however, the hatchability was affected in the group injected with a higher level of nucleosides at 100 mg/egg. The hatched out chicks from higher doses of nucleosides (50 and 100 mg) had higher body weight (BW) (P < 0.05) than the control. Higher energy metabolizability (%) was observed in nucleoside-injected groups. Plasma protein concentration was higher in groups administered with nucleosides (50 and 100 mg). Histologically, the intestinal villi length was maximum in 100 mg-injected group followed by 50 and 25 mg. Relative expression of homeobox (Cdx) in the jejunum was significantly (P < 0.05) upregulated in all the injected groups at 3, 7, and 14 days of age. Nucleoside-administered groups had better performance, energy metabolizability, and intestinal morphology. Among the experimental groups, the administration of nucleosides at 50 mg/egg resulted in higher growth performance, plasma protein, intestinal surface, and villi development in broiler chickens.