Objectives: The present study aimed at assessing psychological flexibility, the core construct of the Acceptance and Commitment Therapy model, in the context of chronic illness. More specifically, the present study aimed at validating the 18-item Portuguese CompACT measure of psychological flexibility in a chronic illness sample (total n = 419; 83.8% women; 16.2% men) collected via online survey. Method: Specifically, we studied the internal structure of the scale employing Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), gender-based invariance, and associations with conceptually relevant constructs (shame, anxiety, depressive symptoms, insomnia severity, and self-compassion). Results: All items from the Openness to Experience subscale were removed due to low loading values on the EFA. The CFA confirmed the adequacy of an 8-item Portuguese CompACT with two subscales, Behavioral Awareness (α = .87) and Valued Action (α = .86). Both subscales correlated negatively with shame, anxiety, depressive symptoms, and insomnia severity. The Valued Action subscale additionally correlated positively with self-compassion. Conclusion: An 8-item version of the Portuguese CompACT, with two subscales, seems to be well suited for application for clinicians with clients with chronic illness.