A 3 × 4 factorial design was used to evaluate the dietary protein requirement and to determine the optimum dietary protein to energy (P/DE) ratio in sub-yearling Persian sturgeon, Acipenser persicus, reared in the indoor system. Twelve experimental diets (40P16, 40P17, 40P18, 40P19, 45P19, 45P17, 45P18, 45P19, 50P16, 50P17, 50P18 and 50P19) were formulated and prepared to contain three protein levels (40%, 45% and 50%) and four digestible energy levels (16, 17, 18 and 19 kJ g−1 diet) at each protein level. Fish averaging 103.3 ± 3.5 (mean ± SD) were fed one of the experimental diets for 14 weeks. At the end of the experimental period, there were significant energy effects (P < 0.05) on weight gain (WG) and specific growth rate (SGR). Weight gain and SGR tended to decrease, although non-significantly, with increase in dietary protein levels. Furthermore, there were significant protein and energy interaction effects on WG, SGR, hepatosomatic index and protein efficiency ratio. However, there were no significant dietary protein, energy or their interaction effects on feed efficiency for fish fed all diets. Weight gain and SGR of fish fed 40P19 were significantly higher than those of fish fed 40P16, 45P16, 45P17, 50P16 and 50P17 diets (P < 0.05). There were no significant differences in WG and SGR among fish fed 40P17, 40P18, 40P19, 45P18, 45P19, 50P18 and 50P19 diets. These results may indicate that the optimum dietary protein requirement and the P/DE ratio could be 40% protein and 22.0 mg protein kJ−1 (40P18), respectively, in Persian sturgeon, based on growth performance and feed utilization.