Objective: The goal of this study was to examine the associations among posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), sleep quality, pain interference, and quality of life in combat veterans. Method: Veterans (N ϭ 289, 86.51% male) completed the Mid-Atlantic MIRECC Assessment of Traumatic Brain Injury, the Clinician-Administered PTSD Scale for DSM-5, and measures of sleep quality, pain interference, and quality of life. Results: Hierarchical linear regressions evaluated associations between PTSD severity, deployment TBI severity, sleep quality, and the outcomes of pain interference and quality of life after adjusting for demographic variables and the number of nondeployment TBIs. PTSD severity, B ϭ 0.15, SE B ϭ 0.04, deployment TBI severity, B ϭ 3.98, SE B ϭ 1.01, and sleep quality, B ϭ 0.74, SE B ϭ 0.13, were significantly associated with pain interference, p Ͻ .001. PTSD severity, B ϭ Ϫ0.57, SE B ϭ 0.07, and pain interference, B ϭ Ϫ0.45, SE B ϭ 0.11, were significantly, independently associated with quality of life, p Ͻ .001. However, pain interference, B ϭ Ϫ0.24, SE B ϭ 0.11, was no longer significantly associated with quality of life when sleep quality, B ϭ Ϫ1.56, SE B ϭ 0.25, was included in the model. There was no significant association between deployment TBI severity and quality of life. Interactions among the studied variables were not significant for either of the outcome variables. Conclusions: PTSD symptom severity, deployment TBI history, and sleep quality may be important to consider in treatment planning for veterans experiencing pain-related functional interference. For veterans with numerous conditions comorbid with pain, treatment plans may include interventions targeting sleep and PTSD to maximize quality of life improvements.