The main objective of this work is to examine low prenatal mood, alcohol and tobacco use and rates of preterm (PTB) and low birth weight (LBW) births among women in Minnesota between 2002 and 2006. We examined the Minnesota version of the national, cross-sectional survey of postpartum women, the Pregnancy Risk Assessment Monitoring System (MN PRAMS). Of the 11,891 women sampled in 2002-2006, 7,457 had complete data for analysis; the weighted response rates averaged 76%. The major variables of interest were: LBW, PTB, maternal mood during pregnancy, prenatal alcohol use, prenatal tobacco use and interaction terms created from the mood and substance use variables. Women with low mood who used tobacco during pregnancy were twice as likely to have a LBW infant as women who did not smoke and reported high mood (AOR = 2.12, 95% CI: 1.35, 3.33, P = 0.001). Among women who abstained from alcohol during pregnancy, those with low mood were at an increased risk for PTB (AOR = 1.95, 95% CI: 1.54-2.45, P < 0.0001) compared to women with high mood. Low maternal mood was associated with increased risks for PTB, and LBW births among MN PRAMS respondents. Substance use and low prenatal mood co-occur and the combined effect on PTB and LBW birth outcomes warrants further investigation.