Red spotted grouper, Epinephelus akaara, is a popular aquaculture species and a protogynous hermaphrodite. Induction of artificial sex change at the time of primary sex differentiation is of interest but has not been successful due to the lack of necessary basic information. To find out the potential neuroendocrine influence on the primary sex differentiation, the expression of key genes in the brain was investigated during the formation of ovarian cavity. Expression of cyp19a1b, esr1, gnrhr1, fsh, lh and cga in the brain was positively associated with the formation of ovarian cavity, showing gradual increase as the formation proceeds. However, the expression of gnrh1 was suppressed during the early part of the ovarian cavity formation, signifying potential hypothalamic influence on the primary sex differentiation in this species.