Depersonalization is common in anxiety disorders, but little is known about factors that influence co-occurring anxiety and depersonalization. We investigated trait moderators of the relationships between state and trait anxiety and depersonalization to better understand their co-occurrence and to identify potential points of intervention. Adults recruited on Amazon Mechanical Turk (N = 303) completed two computer tasks designed to increase variability in state anxiety and depersonalization as well as several self-report questionnaires. As hypothesized (preregistration: https://osf.io/xgazd), anxiety positively predicted depersonalization at both a state level, β = 0.43, 95% CI [0.39, 0.47], and trait level, β = 0.60, 95% CI [0.51, 0.70]. Moreover, as hypothesized, the trait anxiety-trait depersonalization relationship was strengthened by greater anxiety sensitivity, β = 0.25, 95% CI [0.17, 0.34]; distress intolerance, β = 0.15, 95% CI [0.05, 0.25]; and negative interpretation bias for anxiety sensations (inverse transformed), β = -0.21, 95% CI [-0.30, -0.13], and for depersonalization sensations (inverse transformed), β = -0.27, 95% CI [-0.35, -0.19]. None of these hypothesized trait moderators significantly strengthened the state anxiety-state depersonalization relationship.These findings suggest that on a trait level, anxiety and depersonalization more frequently cooccur when people catastrophically misinterpret their symptoms or have lower emotional distress tolerance.