BACKGROUND: Neonatal abstinence syndrome (NAS), or withdrawal from prenatal opioid exposure at birth, can trigger a referral to child protective services (CPS). However, there is some evidence of selection into NAS diagnosis because NAS screening is not universal. Such referrals may protect the infant, help connect the mother to services, or cause harm. OBJECTIVE: To study the relation between prenatal opioid exposure, NAS diagnosis, and CPS involvement during the (early) neonatal period. PARTICIPANTS AND SETTING: We analyzed data (N = 236,868 Medicaid-covered live births) from the Wisconsin Administrative Data Core using linked birth records, Medicaid claims, CPS records, and benefit/earnings data from 2010 to 2018. METHODS: We identified opioid exposure using Medicaid claims and CPS investigations within 7 and 28 days of life. We estimate linear probability models with and without the inclusion of NAS diagnosis and interactions of prenatal opioid exposure and NAS diagnosis. RESULTS: Prenatal opioid exposure is positively associated with CPS involvement, but after controlling for NAS diagnosis, exposure to opioid medications used to treat pain (non-MOUD) or opioid use disorder (MOUD) are not statistically significantly associated with CPS investigations, whereas illicit opioid exposure is associated with increased CPS investigations. Fully interacted models suggest that, for infants diagnosed with NAS, non-MOUD and MOUD exposure are protective and reduce the likelihood of CPS involvement. CONCLUSIONS: Understanding the type of opioid exposure during pregnancy, NAS diagnosis, and access to treatment OUD is important for referrals to child welfare agencies.