Current guidelines recommend that pregnant women should not take efavirenz, since animal studies of efavirenz showed high rates of birth defects. Three out of 20 monkeys administered efavirenz during pregnancy gave birth to babies with significant abnormalities.

However, efavirenz has never been tested in humans and the implications for humans are unknown. In early 2002, there was a report of an infant accidentally exposed to efavirenz during the early phase of gestation who was born with severe abnormalities attributed to neural tube defects^[1]. There have also been four further reports of neural tube defects children born to women exposed to efavirenz during the first three months of pregnancy, which led the manufacturer and the United States Food and Drug Administration to recommend in March 2005 that pregnant women avoid the drug. However, it is difficult to be certain on the risks of the drug causing these birth defects, and whether their incidence is greater than would be expected in women not taking efavirenz.

Although a causal relationship has not been established between efavirenz and birth defects, women on efavirenz are advised to use barrier contraception for vaginal sex, and should also use oral contraceptives or another form of contraception. It is not known whether efavirenz passes into breastmilk. As such, efavirenz is not recommended for breastfeeding mothers.