Objective: To investigate whether there is an association between sudden infant death syndrome (SIDS) and perinatal depression. Method: A case-control study design was used. Cases included women registered in a British primary care database with a live birth (1987-2000) and a subsequent SIDS death. Controls were women with a live birth born in the same year as the matched SIDS death, with infant survival for the first year of life. Results: One hundred sixty-nine linked mother-infant cases of SIDS were matched with 662 mother-infant controls. The authors found that SIDS was independently associated with maternal depression in the year before birth (odds ratio [OR] = 4.93, 95% CI = 1.10 to 22.05), smoking (OR = 2.50, 95% CI = 1.29 to 4.88), and male sex (OR = 1.94, 95% CI = 1.04 to 3.64). There was weak evidence of an independent association of SIDS with depression in the 6 months after birth, before the index SIDS death (OR = 1.80, 95% CI = 0.71 to 4.56). Conclusion: This study provides further evidence for an association between SIDS and perinatal depression, particularly antenatal depression. Health care professionals should ensure that women with perinatal depression are appropriately treated and are provided with clear advice on infant care practices that may prevent SIDS.