ABSTRACT Research has found that difficulties in emotion regulation negatively impact mental health, whereas cognitive flexibility may promote stress resilience and positive mental health. Little is known about cognitive flexibility and emotion regulation in people with comorbid eating disorder (ED) and anxiety and stress disorders. A transdiagnostic ED population (N = 227) at an outpatient ED treatment facility completed several self-report instruments that measured cognitive flexibility, emotion regulation difficulties, posttraumatic stress disorder (PTSD) symptoms, and generalized anxiety disorder (GAD) symptoms upon admission. We investigated cognitive flexibility and emotion regulation differences for those with an ED without comorbidity and those with various combinations of comorbidity. In a one-way between-groups ANOVA, we investigated differences in cognitive flexibility for those with GAD, PTSD, neither, and both comorbidities. We found a statistically significant difference between these groups, with mean cognitive flexibility inventory scores being the lowest in the group with both comorbidities. However, when controlling for emotion regulation, a one-way between-groups ANCOVA indicated no significant differences in cognitive flexibility between comorbidity groups F(3, 222) = 1.20, p = .31 Partial η 2 = .02. Though self-reported cognitive flexibility levels differ among ED patients with and without comorbidities, it appears that these differences are better explained by emotion regulation. Therefore, addressing emotion regulation early in treatment for all individuals with EDs, regardless of comorbidity, is recommended as a future research focus to enhance treatment outcomes. Further research is needed to understand the impact of treating emotion regulation on ED treatment engagement, dropout, and effectiveness.