Artificial insemination, performed to maximize genetic diversity in populations of zoo-housed animals, requires intensive management and has been associated with low success rates in fractious species. In these species, stressors, such as frequent handling, may impact fertility. Long-acting neuroleptic pharmaceuticals (LANs) can attenuate the stress response to handling, but may also disrupt ovulation in some species, compromising their use for artificial insemination. Therefore, the goal of this study was to determine whether LANs may be used to mitigate stress during reproductive management in wild equids without inhibiting ovulation. Six female Persian onagers (Equus hemionus onager) were treated with fluphenazine decanoate (FD; 0.1 mg/kg IM) or saline control in a random crossover design study. Urinary cortisol, progesterone, estrogen metabolites and behavior were monitored, and follicular dynamics were examined using ultrasonography until ovulation. Onagers demonstrated significantly lower cortisol concentrations (P = 0.03) when treated with FD (6.61 ± 3.26 ng/mg creatinine) compared to saline (9.73 ± 3.19 ng/mg creatinine). Overall, there were no differences in peak estrogen (P = 0.51) or progesterone (P = 0.38) concentrations between the two groups, and all animals ovulated within the expected time frame following FD treatment. However, some onagers exhibited only minor reductions in cortisol secretion and one treated female demonstrated a suppressed luteal progesterone peak, indicating a possible reproductive cost to FD administration. While FD may be useful for highly fractious equids for which the stress of handling delays or inhibits ovulation, these results warrant further investigation of dosing.