Background: Poor sleep is common in the ICU setting and may represent a modifiable risk factor for patient participation in ICU-based physical therapy (PT) interventions. This study evaluates the association of perceived sleep quality, delirium, sedation, and other clinically important patient and ICU factors with participation in physical therapy (PT) interventions. Method: This was a secondary analysis of a prospective observational study of sleep in a single academic medical ICU (MICU). Perceived sleep quality was assessed using the Richards-Campbell Sleep Questionnaire (RCSQ) and delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Other covariates included demographics, pre-hospitalization ambulation status, ICU admission diagnosis, daily mechanical ventilation status, and daily administration of benzodiazepines and opioids via bolus and continuous infusion. Associations with participation in PT interventions were assessed among patients eligible for PT using a multinomial Markov model with robust variance estimates. Results: Overall, 327 consecutive MICU patients completed ≥1 assessment of perceived sleep quality. After adjusting for all covariates, daily assessment of perceived sleep quality was not associated with transitioning to participate in PT the following day (relative risk ratio [RRR] 1.02, 95 % CI 0.96-1.07, p = 0.55). However, the following factors had significant negative associations with participating in subsequent PT interventions: delirium (RRR 0.58, 95 % CI 0.41-0.76, p <0.001), opioid boluses (RRR 0.68, 95 % CI 0.47-0.99, p = 0.04), and continuous sedation infusions (RRR 0.58, 95 % CI 0.40-0.85, p = 0.01). Additionally, in patients with delirium, benzodiazepine boluses further reduced participation in subsequent PT interventions (RRR 0.25, 95 % CI 0.13-0.50, p <0.001). Conclusions: Perceived sleep quality was not associated with participation in PT interventions the following day. However, continuous sedation infusions, opioid boluses, and delirium, particularly when occurring with administration of benzodiazepine boluses, were negatively associated with subsequent PT interventions and represent important modifiable factors for increasing participation in ICU-based PT interventions.