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Chronic fatigue syndrome (CFS) presents challenges in differential diagnosis and treatment. Complicating diagnosis is that its symptoms overlap with those of depression. This study applies psychoanalytic concepts to understand emotional regulation (ER) in women with CFS and/or depression. One hundred eighty-six women were assigned to four groups and compared: (a) CFS plus high er depression (CFS-HD); (b) CFS plus lower depression (CFS-LD); (c) depressive disorder (DD); and (d) healthy controls (HC). ER was operationalized by measures of capacity to form internal representations and adaptive defenses. The study's premise was that difficulties metabolizing emotions psychologically would be associated with their greater somatic expression. Some support was found for the hypothesis that CFS participants would exhibit more impairment in representing emotions and in adaptive defenses compared to the DD and HC groups, but this held only for the CFS-HD group. Although CFS-LD participants were expected to be more purely somatizing than the CFS-HD group, they instead showed more sophisticated capacities for ER than that group and recalled less distressing early relationships, revealing more resilience. Still, however, we found support for somatization in some CFS sufferers: Within both the CFS-HD and the CFS-LD groups, weaknesses in representing emotions and in defensive functioning were associated with more severe physical symptoms. Clinically, the heterogeneity of CFS and those who suffer from it indicates the need for individual assessment and depression treatment.