Abstract Background Since the onset of the COVID-19 pandemic, Belgium has been hit by a series of surges in the number of COVID-19 cases. Each of these resulted in more stringent measures being taken to curb the pandemic. This study compared perception of and adherence to COVID-19 measures of the Belgian population at two time periods: September 2020 (survey 1) and April/May 2021 (survey 2). Methods Two samples of approximately 2000 participants, representative for the Belgian population in terms of gender, age, province and socio-economic status, participated in an online survey. The survey questionnaire measured the perceived infection risk and severity, and the perception of and adherence to protective measures. Answers were compared between the time periods and risk factors for lower adherence were identified using multivariate linear regression. Results In survey 2, at which time the measures were more stringent, respondents assessed the risk of infection for themselves as lower, and for parents and grandparents as higher than in survey 1. Scores for understanding and usefulness of the measures were higher in survey 2 compared to survey 1, while reported past and future adherence were lower. Risk factors for a lower adherence were being male, being young, speaking French vs. Dutch, and having undergone a symptomatic infection. Conclusions It is important to consider the potential effect of fatigue among the population with regards to measures that are sustained for a long time, especially regarding measures related to social contacts. The identified risk factors for lower adherence offer insights to policy makers for future crisis communication regarding COVID-19.