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Objective Immunocompromised patients with chronic inflammatory diseases (CID) may have experienced additional psychosocial burden during the COVID‐19 pandemic due to an immunocompromised status. We hypothesized that vaccination will result in improved patient‐reported outcomes (PROs) longitudinally among individuals with CID undergoing SARS‐CoV‐2 vaccination following vaccination regardless of baseline anxiety. Methods Data are from a cohort of individuals with CID from two sites undergoing SARS‐CoV‐2 vaccination. Participants completed three study visits before and after two mRNA vaccine doses, in the initial vaccination series, where clinical data was collected. PROs were measured using the PROMIS‐29 Profile and expressed as T‐scores, with 2 groups stratified by high and low baseline anxiety. Mixed effects models were used to examine longitudinal changes, adjusting for age, gender, and study site. Results The cohort was 72% female with mean ±SD age of 48.1±15.5 years. Overall, sleep disturbance improved following both doses of SARS‐CoV‐2 vaccinations and anxiety decreased after the second dose. Physical function scores worsened but did not meet MID threshold. Stratifying by baseline anxiety, improvement in anxiety, fatigue, and social participation were greater for the high anxiety group. Physical function worsened slightly for both groups and sleep disturbance improved significantly in the high anxiety group. Conclusion Sleep disturbance decreased in a significant and meaningful way in patients with CID upon vaccination. In patients with higher baseline anxiety, social participation increased and anxiety, fatigue, and sleep disturbance decreased. Overall, results suggest that SARS‐CoV‐2 vaccines may improve mental health and wellbeing, particularly among those with greater anxiety.

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