Background: Post-operative hypoxemia is prevalent in hospitalized patients and may adversely affect recovery. However, little data exist on the post-discharge phase or details on duration, severity and potential risk factors. Thus, we investigated the incidence and risk factors for severe desaturation during the first post-operative week after THA/TKA by continuous nocturnal oxygen saturation monitoring. Methods: The study was a secondary analysis of a prospective cohort study of 112 patients undergoing fast-track THA/TKA. Patients with known sleep apnoea were excluded. Oxygen saturation and heart rate were recorded by a wireless wrist-worn pulse oximeter 2 nights before and 7 nights after surgery. Data on demographics, opioid consumption and cognitive function were collected from medical charts, patient diaries and clinical testing respectively. The primary outcome was occurrence of severe desaturation defined as periods with saturation <85% lasting ≥10 minutes. Secondary outcomes included description of various saturation levels and relevant risk factors. Results: Severe oxygen desaturation occurred in 35% of the patients during the first post-operative week. Duration and severity of hypoxemic episodes increased after the first post-operative day. Pre-operative episodes of hypoxemia significantly increased the risk of post-operative hypoxemic events (OR 2.4-4.4, CI 0.4-46), while pre- and post-operative opioid use, age, gender, ASA classification, type of surgery or anaesthesia were significantly related to the development of post-operative hypoxemia. Conclusions: One third of the patients suffered from increased and prolonged episodes of severe nocturnal hypoxemia during the first week after THA/TKA discharge. Increased risk for severe hypoxemic episodes was related to pre-operative hypoxemia.