Abstract Background Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course. Methods Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May–October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness. Results Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 33%), rectal bleeding (n = 27 24%), or severe pain (n = 24 21%). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (−5.5 days, P = .04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P = .66). Early tecovirimat was not associated with faster illness resolution, regardless of severity. Conclusions Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding. We interviewed 115 persons with mpox who did and did not receive tecovirimat, and performed a multivariable regression analysis. Initiating tecovirimat within 5 days of symptom onset appeared to be associated with faster improvement of symptoms in patients with severe mpox.