There are limited studies comparing the health utility values of EQ-5D-5L and SF-6Dv2 within the same patient cohorts. The widespread transmission and recurring infections associated with Omicron variants amid the COVID-19 pandemic have resulted in substantial health detriments and increased utilisation of health care resources. This highlights the crucial need to assess the loss in quality-adjusted life years (QALYs). Therefore, this study aims to compare the ceiling and floor effects, agreement, correlation and responsiveness between EQ-5D-5L and SF-6Dv2 based on COVID-19 patients during the Omicron outbreak in China. We recruited 694 COVID-19 patients across mainland China to participant in an online questionnaire survey from January to February 2023. The questionnaire encompassed queries concerning the sociodemographic and health details of the participants, who were requested to recollect their health status during and after experiencing COVID-19 using the EQ-5D-5L and SF-6Dv2 questionnaires. Epanechnikov kernel density plots were used to visualise the ceiling and floor effects for both instruments. Agreement was assessed by Bland-Altman graph and intraclass correlation coefficient (ICC). Correlation was evaluated using linear regression, Pearson's correlation and Spearman's correlation. The standardised response mean (SRM) and relative efficiency (RE) were used to examine the responsiveness of EQ-5D-5L and SF-6Dv2 at detecting the health improvement after COVID-19 infection and the difference in dichotomous health indicators. In total, 648 valid responses from patients aged 35.6 ± 15.0 years were involved in analysis. The EQ-5D-5L utility indices were 0.58 ± 0.33 and 0.92 ± 0.14 during and after COVID-19 infection, respectively, which were significantly higher than indices of the SF-6Dv2 utility (0.43 ± 0.31 and 0.81 ± 0.19, p < 0.001). A ceiling effect of EQ-5D-5L larger than that of SF-6Dv2 was observed during COVID-19 infection (49.5% vs 21.6%). Intraclass correlation coefficients between EQ-5D-5L and SF-6Dv2 during and after COVID-19 infection were 0.69 and 0.55, respectively. The utility indices of EQ-5D-5L and SF-6Dv2 were highly correlated, with Pearson's correlation coefficients of 0.76 and 0.70 (p < 0.001) during and after COVID-19 infection, respectively. The spearman's correlations were moderate to high between dimensions of EQ-5D-5L and SF-6Dv2 (p < 0.01). Both EQ-5D-5L and SF-6Dv2 were responsive to detect health improvement after COVID-19 and the differences in dichotomous health indicators. The utility indices generated by EQ-5D-5L and SF-6Dv2 in COVID-19 patients demonstrate strong correlation and responsiveness. However, the agreement between these two instruments does not reach a satisfactory level. Consequently, these two measures cannot be used interchangeably. In situations where apprehensions about ceiling effects affecting outcome measurement arise, it is advisable to consider SF-6Dv2 as a preferable outcome measure for studies on patients with COVID-19.