Effect of booster vaccination and vitamin D status on antibody production of Omicron variant-infected adults need to be further explored. A retrospective, longitudinal, real-world cohort study was performed. All included cases were divided into vitamin D deficiency (VDD) and non-VDD (control) groups according to baseline serum 25-hydroxyvitamin D [25(OH)D] concentration and then into unvaccinated, routinely vaccinated, and booster vaccinated VDD and control subgroups according to vaccination status. Antibody dynamics were observed within six time periods during hospitalization. A total of 204 adult cases were included, of which 121 (59%) were males; 23 (11%), 31 (15%), and 26 (13%) or 50 (25%), 35 (17%), and 39 (19%) were unvaccinated, routinely vaccinated, and booster vaccinated VDD cases or controls, respectively. The median (interquartile range) for age and baseline 25(OH)D concentration was 42.5 (31-53.5) years and 21.5 (18-25.4) ng/mL, respectively. The IgM titers within 3 to 7days and 7 to 14 days increased rapidly to 1.8-fold (P < 0.001) and 3.6-fold (P < 0.001) those within the first day; the IgG titers increased to 5.8-fold (P < 0.001) and 10.9-fold (P < 0.001). Booster vaccinated controls had higher first IgG titers compared with unvaccinated controls (3.1-fold; P = 0.001) or booster vaccinated VDD cases (2.1-fold; P = 0.02). Booster vaccination and non-VDD status may have an interactive boosting effect on IgG production of Omicron variant-infected adults. Further randomized clinical trials may be needed to determine whether booster vaccination combined with VDD correction improves the humoral immunity to Omicron variants.