Additional Study Information: We are looking for adult volunteers with presumed or confirmed monkeypox infections to help us see if tecovirimat (TPOXX) is a safe and effective treatment for monkeypox. Human Monkeypox Virus is currently the cause of an outbreak in the US and throughout the world, leading the World Health Organization to declare it a public health emergency of international concern. Tecovirimat, an oral medication that is FDA-approved to treat smallpox, is thought to have activity against monkeypox, based on small studies in animals and humans. This study will assess the safety and effectiveness of tecovirimat in treating monkeypox infections in adults with presumed or confirmed monkeypox infections. The study will include a placebo arm; approximately 530 participants will be randomly assigned in a 2:1 ratio to receive tecovirimat pills (Arm A of the study) or matching placebo pills (Arm B) for 14 days. An additional approximately 250 individuals who meet specific study criteria (including study-defined severe disease or severe immunosuppression) will be given open-label tecovirimat (Arm C). Participants in Arms A and B who have severe pain after 5 days of treatment, or who progress to the study-defined severe disease will be offered open-label tecovirimat. Participants will have weekly follow-up visits for the first four weeks, and then one final study visit at day 57. Individuals who join the study will be compensated for their time for in-person study visits. If you have suspected or confirmed monkeypox, you may be eligible to participate. Not sure if you are eligible? Take the first step and request to be contacted by our study team.