Background: Early emotional neglect can have long-term effects on physical health through psychobiological mechanisms. Attachment insecurity, in addition to other factors, could serve as a mediating factor in this association. In Wochenkrippen (day and night nurseries) in the former German Democratic Republic (GDR), infants were raised in a residential care setting throughout the week, which was associated with a high risk of early emotional deprivation. The cohort of former Wochenkrippenkinder (weekly nursery children) offers a unique opportunity to investigate the relationships between early emotional deprivation, attachment insecurity and physical health in adulthood. Objective: Is the experience of day and night nursery care associated with greater physical disease burden and is this association mediated by attachment insecurity? Furthermore, what associations can be identified with current levels of depression, anxiety and maladaptive health behavior? Methods: A total of N = 294 former day and night nursery children (WKG) and N = 222 control participants (KG) completed self-report questionnaires assessing medically diagnosed conditions (disease burden), attachment insecurity, current psychological distress and health behavior. Mediation analyses were conducted to examine the relationships among these variables. Results: Compared to the KG, the WKG participants reported a higher burden of physical illness, greater attachment anxiety and avoidance as well as increased levels of depression and anxiety. The association between day and night nursery care and the physical illness burden was mediated by insecure attachment experiences and symptoms of depression and anxiety, with differential effects observed for attachment anxiety and avoidance. No associations were found between day and night nursery care and health-related behavior. Conclusion: Attachment insecurity could play a key role in mediating the link between early emotional neglect and the risk of physical illness across the lifespan, both directly and indirectly through psychological distress. Assessing attachment experiences and early nonfamilial caregiving should be more strongly integrated into medical history taking.