Background: Individuals with chronic disease or disability (CDD) were particularly vulnerable to mental health issues during the COVID-19 health crisis. This study aimed to assess the association between anxiety symptoms and the severity of non-pharmaceutical interventions (NPIs) during the COVID-19 health crisis in France, and to identify factors influencing anxiety levels among people with CDD. Methods: We conducted a monthly longitudinal survey between 20 May 2020 and 31 May 2023 among volunteer participants with CDD recruited by health association networks. Anxiety was measured using the Generalized Anxiety Disorder scale (GAD-7). Each of 11 pandemic periods was assigned a ‘NPI severity’ level, ranging from 0 (least restrictive) to 4 (most restrictive). Results: A total of 3713 individuals with CDD completed 41,678 questionnaires. Anxiety symptoms (GAD-7 ≥ 8), included mild-to-moderate symptoms, were associated with several NPIs severity levels, with an odds ratio of 1.22 (95%CI: [1.10 - 1.35]) for NPI level 2, 1.49 (95% CI: [1.34 - 1.66]) for level 3, and 1.38 (95%CI: [1.23 - 1.55]) for level 4, compared to level 0. Women, people aged 18–49 years, individuals with low socioeconomic status, multiple comorbidities, and difficulties with continuity of care, had a higher risk of anxiety symptoms. Limitations: The results cannot be generalized to the entire French CDD population and no pre-crisis data were available for comparison. Conclusion: Our study highlights a link between NPIs severity during the COVID-19 health crisis and the risk of anxiety symptoms in individuals with CDD. The psychological effects of NPIs should be considered in future pandemic interventions.