Background <p>Post-COVID-19 condition is an ongoing public health concern, and the lack of established treatments increases health care utilization. Recent evidence suggests that cognitive and behavioral approaches reduce symptoms and improve functional capabilities. This study reports the cost-effectiveness of a brief outpatient cognitive-behavioral rehabilitation program compared to care as usual in non-hospitalized patients with post-COVID-19 condition.</p> Methods <p>An economic evaluation based on a randomized clinical trial was conducted from a health care sector perspective. Health care utilization was charted using a self-developed questionnaire administered immediately after the intervention as well as 12 months after inclusion. Health-related quality of life was measured using the EQ-5D-5L inventory at inclusion and follow-ups and valued using the Norwegian tariff. We used multiple imputation with chained equations to impute missing data. To illustrate analysis of uncertainty, bootstrapping was performed. To account for correlation between costs and quality-adjusted life years (QALYs), we conducted seemingly unrelated regression. Costs and QALYs were summarized over the entire 12-month follow-up period.</p> Results <p>Over 12 months, analysis yielded an incremental QALY gain of 0.056 (95% CI: 0.024 to 0.077) and an overall cost reduction of NOK − 20,682 (95% CI: -47230 to -1614) per patient receiving the brief outpatient rehabilitation program compared to care as usual. A total of 100% of simulations indicated that the intervention was cost-effective.</p> Conclusion <p>A brief outpatient rehabilitation program based on a cognitive and behavioral approach was cost-effective compared to care as usual in non-hospitalized patients with post-COVID-19 condition. Further investigations of comparable clinical trials within other health care systems are warranted.</p> Trial registration <p>ClinicalTrials.gov Identifier: NCT05196451, 19th January 2022.</p>