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To investigate the associations of weekend catch-up sleep (WCS) and high-sensitivity C-reactive protein (hs-CRP) levels according to bedtime inconsistency in the Korean population. In this cross-sectional study using the Korea National Health and Nutrition Examination Survey (2016–2018) with 17,665 participants, four groups were defined: no-WCS (WCS within ± 1 h of weekday sleep time), moderate WCS (1 ≤ , < 3 h), severe WCS (≥ 3 h), and inverse WCS (≤ − 1 h). An inconsistent bedtime was defined as a > 2 h difference between weekend and weekday bedtimes. Outcomes were divided into quartiles based on the hs-CRP level: Lowest (< 0.34), Middle-low (≥ 0.34, < 0.55), Middle-high (≥ 0.55, < 1.10), Highest (≥ 1.10). Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using multinomial logistic regression, controlling for relevant covariates. Moderate WCS was associated with a lower risk for the highest hs-CRP levels than no WCS (aOR = 0.87, 95% CI 0.78–0.97), and a similar association was observed only in participants with consistent bedtimes (aOR = 0.88, 95% CI 0.78–0.99). Significant interactions of those associations of WCS and hs-CRP levels with bedtime inconsistency were found. These findings provide evidence that people with inconsistent bedtimes would have limited protective effect of WCS on hs-CRP. [ABSTRACT FROM AUTHOR]