Background: The impact of COVID-19 infection on workers' work function persists even after the acute phase of the infection. We studied this phenomenon in Japanese workers. Methods: We conducted a one-year prospective cohort study online, starting with a baseline survey in December 2020. We tracked workers without baseline work functioning impairment and incorporated data from 14,421 eligible individuals into the analysis. We estimated the incidence rate ratio for new onset of work functioning impairment due to COVID-19 infection during follow-up, using mixed-effects Poisson regression analysis with robust variance. Results: Participants reporting infection between January and December 2021 showed a significantly higher incidence of new work functioning impairment (adjusted incidence rate ratio: 2.18, 95% confidence interval: 1.75–2.71, p < 0.001). The formality of the recuperation environment correlated with a higher risk of work functioning deterioration in infected individuals (p for trend <0.001). Conclusion COVID-19-infected workers may continue to experience work difficulties due to persistent, post-acute infection symptoms. Companies and society must urgently provide rehabilitation and social support for people with persistent symptoms, recognizing that COVID-19 is not just a transient acute infection.