The objective of this study was to test the hypothesis that higher daily opioid dose is associated with the presence and severity of neonatal abstinence syndrome (NAS) in pregnant women with sickle cell disease (SCD). This was a retrospective study of pregnant women with SCD who required opioids. NAS was evaluated using the Finnegan scoring system and classified as none, mild, and severe. Severe NAS was defined as a Finnegan score≥8 on 3 consecutive tests. Thirty-four pregnancies were examined in 30 women with SCD. Higher daily morphine dose was associated with a higher percentage of days in the hospital during pregnancy (P<0.001). Hospital days contributed disproportionately to daily morphine dose as larger amounts of opioids were administered in the hospital compared to home (P=0.002). Median maternal oral morphine dose was 416 mg for infants with severe NAS compared with 139 mg for those with mild NAS (P=0.04). For infants with no NAS, median maternal morphine was 4 mg, significantly less than those with mild NAS (P<0.001). Infants born to women who used on average >200 mg/day of oral morphine equivalent in the last month of pregnancy had a 13-fold increased risk of severe NAS compared with those who used <200 mg/day. These data demonstrate that higher median daily opioid dose is associated with progressively more severe NAS in pregnant women with SCD. Strategies to decrease pain and avoid hospitalizations are needed to reduce opioid use and NAS. Am. J. Hematol. 91:416-419, 2016.