To deepen our understanding of peripartum mood concerns in women with multiple sclerosis (MS) by assessing the prevalence and temporal pattern of prospectively collected perinatal depression and anxiety as well as contributing risk factors. Women with neurological conditions may be at higher risk of peripartum depression (PPD) and anxiety, including in MS. The relationship between prospectively collected mood outcomes and postpartum MS clinical course is unknown. PRISMA is an ongoing prospective registry of women with MS who are pregnant, contemplating pregnancy, or postpartum. For the current analysis, data on the first 53 participants were analyzed. Data include structured depression assessments (MINI/SCID), and serial surveys: Edinburgh Postnatal Depression Scale (EPDS), Hospital Anxiety and Depression Scale (HADS), and sleep (Epworth Sleepiness Scale). Among this cohort (n= 53), 71% were non-Hispanic White; median pre-conception EDSS was 1.5 (IQR 1-2.5). The prevalence of depression (MINI/SCID) at any point in the first 12 months postpartum was 19.51%. The time point with the highest % of EPDS scores of 10 or above was at 1 month postpartum (19%); of these, 78% normalized by 4 months. One month postpartum EPDS scores were correlated with HADS-Anxiety (r=0.68, p<0.05) and HADS-Anxiety scores (r=0.71, p < 0.05). Four month postpartum EPDS scores were correlated with HADS-Depression scores (r=0.68, p<0.05) and HADS-Anxiety scores (r=0.64, p<0.05). Higher EPDS scores were also associated with preconception history of psychiatric disease, but were not correlated with MRI gadolinium positivity or with clinical relapses in the first 3M postpartum. The prevalence of depression in the first 12 months postpartum in this current study was 19.5%, which is higher than the general population and in line with a prior report in MS. The peak incidence at the 1 month postpartum time point suggests the need for early evaluation postpartum and integration of neurological, obstetrical, and psychological care. Disclosure: Miss Rose has nothing to disclose. Ms. Hsu has nothing to disclose. Miss Balan has nothing to disclose. Annika Anderson has received personal compensation for serving as an employee of University of California, San Francisco. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. The institution of Dr. Bove has received research support from Eli Lilly.