The COVID-19 pandemic caused significant health distress among autistic adults in the United States. While there is considerable evidence that autistic adults' COVID-19 health distress was related to increases in mental health concerns (e.g. depression, anxiety, and stress), there is a less clear understanding of the possible mechanisms by which this process occurs. Accordingly, our participatory action research team assessed whether psychological flexibility, a strengths-based mechanism from acceptance and commitment therapy, mediated the association between COVID-19-related health distress and mental health concerns (e.g. depression, anxiety, and stress). We found that among 281 autistic adults the positive relationship between COVID-19 health distress and mental health concerns was partially mediated by values progress (a component of psychological flexibility) and values obstruction (a component of psychological inflexibility). Results provide preliminary support that the strengths-based mechanism of psychological flexibility might be a salient therapeutic target to improve mental health among autistic adults experiencing health distress.