Objectives: In this preliminary, longitudinal study, our objective was to assess changes in sleep quality during an inpatient stay in a rehabilitation setting in the United States and to relate changes to patients’ demographic and clinical characteristics (i.e., age, gender, BMI, ethnicity, reason for hospitalization, pre-hospital living setting, prior diagnosis of sleep disorders, and mental health status). Methods: A total of 35 patients participated in this preliminary study (age = 61 ± 16 years old, 50% <65; BMI = 30 ± 7 kg/m2; 51% female; 51% Caucasian). The average length of hospitalization was 18 ± 8 days. Reasons for hospitalization included orthopedic-related issues (28%), spinal cord injury (28%), stroke (20%), and other (23%). In this sample, 23% had prior sleep disorders (mostly sleep apnea), and 60% came from an acute care unit. Patients’ sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) at admission and before discharge. Demographic and medical data were collected. Patients’ mental health status was also assessed at the same intervals. Nighttime sound levels and the average number of sleep disturbances were also collected throughout the study (6 months). Results: Our data revealed that most patients had poor sleep (PSQI > 5) at admission (86%) and discharge (80%). Using a repeated ANOVA, a significant interaction was obtained between sleep quality and the presence of a diagnosed sleep disorder [F (1, 33) = 12.861,p= 0.001, η2p= 0.280]. The sleep quality of patients with sleep disorders improved over their stay, while the sleep of patients without such disorders did not. The mean nighttime sound collection level averages and peaks were 62.3 ± 5.1 dB and 86.1 ± 4.9 dB, respectively, and the average number of sleep disturbances was 2.6 ± 1.1. Conclusion: The improved sleep observed in patients with vs. without sleep disorders might be related to the care received for treating such disorders over the stay. Our findings call for the better detection and management of poor sleep in acute inpatient rehabilitation settings. Furthermore, if our findings are replicated in the future, studies on the implementation of quiet times for medical staff, patients, and family should be performed to improve sleep quality in the inpatient rehabilitation setting.