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It is unclear how the risk of post-COVID symptoms evolved during the pandemic, especially before the spread of Severe Acute Respiratory Syndrome Coronavirus 2 variants and the availability of vaccines. We used modified Poisson regressions to compare the risk of six-month post-COVID symptoms and their associated risk factors according to the period of first acute COVID: during the French first (March-May 2020) or second (September-November 2020) wave. Nonresponse weights and multiple imputation were used to handle missing data. Among participants aged 15 years or older in a national population-based cohort, the risk of post-COVID symptoms was 14.6% (95% confidence interval [CI], 13.9%-15.3%) in March-May 2020, vs 7.0% (95% CI, 6.3%-7.7%) in September-November 2020 (adjusted relative risk [RR], 1.36; 95% CI, 1.20-1.55). For both periods, the risk was higher in the presence of baseline physical condition(s), and it increased with the number of acute symptoms. During the first wave, the risk was also higher for women, in the presence of baseline mental condition(s), and it varied with educational level. In France in 2020, the risk of six-month post-COVID symptoms was higher during the first than the second wave. This difference was observed before the spread of variants and the availability of vaccines., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)