Non-pharmaceutical interventions (NPIs) are essential for controlling infectious diseases during pre-vaccine periods, yet their success hinges on sustained public adherence. This study investigates adherence dynamics to tiered restriction systems implemented during COVID-19 in six geographical regions across Europe, North America, Africa, and South America. Using daily mobility data and linear-mixed models, we assessed three types of fatigue: overall fatigue (linked to cumulative time under restrictions), tier fatigue (linked to time spent under a specific tier), and iteration fatigue (linked to repeated implementation of the same tier). Tier fatigue caused the most rapid adherence loss, producing effects within days that overall fatigue required months of restrictions to achieve. Iterative application of shorter NPIs, interspersed with temporary relaxation, helped reset adherence, mitigating fatigue and sometimes even improving compliance. Psychological relief and a sense of regained autonomy during relaxation periods may renew public willingness to comply when restrictions are reintroduced. These findings emphasize the dual benefits of short, strategic NPIs for epidemic control and public resilience, offering actionable insights for designing more sustainable pandemic interventions.

The authors have declared no competing interest.

The authors thank Shweta Bansal for useful discussions on this study. The research was partially supported by: ANR grant DATAREDUX (ANR-19-CE46-0008-03) to LDD, CES, VC; EU Horizon 2020 grant MOOD (H2020-874850, publication cataloged as MOOD 124) to AR, CES, VC; EU Horizon Europe grant VERDI (101045989) to VC; EU Horizon Europe grant ESCAPE (101095619) to AR, VC; Telefonica R&D Chile and CISCO Chile to LF; FONDECYT Grant N1221315 to LF; Lagrange project of the ISI Foundation funded by Fondazione CRT to LF. The contents of this publication are the sole responsibility of the authors and don't necessarily reflect the views of the European Commission.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study utilises anonymized, unidentifiable data collected from individual mobile phone devices and publicly available aggregated case count data in Chile. It does not use or access individual personal information, and has therefore been waived for an ethical approval. This decision was made by the Institutional Ethics Committee at Universidad del Desarrollo, Santiago de Chile, Chile, communicated to the authors on March 30, 2022.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data from Google mobility reports are publicly available. Mobility data for Chile produced in the present study are available upon reasonable request to the authors.

https://www.google.com/covid19/mobility/