Menopause is the permanent cessation of menstruation that results from depletion of ovarian germ cells and follicles. Although most animals experience reproductive senescence, the mechanisms differ from that in women, who may live more than one-third of their lives after menopause and consequently face the risk of a number of menopause-associated health problems. Understanding factors that influence ovarian aging may provide strategies to delay or alleviate physiological alterations that take place in postmenopausal women. The germ cell-deficient Wv mice recapitulate follicle loss, prolong postreproductive lifespan, and model many physiological changes that take place in postmenopausal women. Here, using genetic and pharmacological approaches, we found that inhibition of cyclooxygenase-1 but not cyclooxygenase-2 in Wv mice delays germ cell depletion and preserves ovarian follicles. Cyclooxygenase-1 inhibition slows down follicle maturation at the conversion of primary to secondary follicles and prolongs postnatal ovarian follicle lifespan. The current study suggests that inhibition of cyclooxygenase-1 may be able to delay ovarian aging and modulate menopausal timing.