OBJECTIVE Best practices for addressing women's mental health and screening for depression in public health clinics are not available. Clinic staff are often responsible for screening for depression; however, few studies examine staff perceptions on feasibility and acceptability of using perinatal screening for mood disorders in ethnically diverse public health clinics. METHODS During December 2012, we conducted four focus groups using a semistructured interview guide with public health clinic staff of varying disciplines (n=25) in a Special Supplemental Nutrition Program for Women, Infants, and Children. All interviews were audio recorded and analyzed using thematic analysis. RESULTS We found five descriptive themes related to acceptability and feasibility of screening for perinatal depression in a public health clinic. The main themes include (1) literacy barriers, (2) need for referrals and follow-up with outside services, (3) training and capacity needs, (4) stigma of depression, and (5) location and privacy of screening. Although multiple barriers to universal depression screening in a public health clinic were identified, participants found value in practice of screening low-income women for depression. CONCLUSION Factors for facilitating implementation of systematic depression screening in a public health clinic have been identified. Implications discuss how policy makers and public health clinic administrators can improve the universal depression screening process.