OBJECTIVES/GOALS: To examine the individual and combined association between preoperative sleep disturbance (SD) and depression and 12-month disability, back pain, and leg pain after lumbar spine surgery (LSS). METHODS/STUDY POPULATION: We analyzed prospectively collected multi-center registry data from 700 patients undergoing LSS (mean age=60.9 years, 37% female, 89% white). Preoperative SD and depression were assessed with PROMIS measures. Established thresholds defined patients with moderate/severe symptoms. Disability (Oswestry Disability Index) and back and leg pain (Numeric Rating Scales) were assessed preoperatively and at 12 months. We conducted separate regressions to examine the influence of SD and depression on each outcome. Regressions examined each factor with and without accounting for the other and in combination as a 4-level variable. Covariates included age, sex, race, education, insurance, body mass index, smoking status, preoperative opioid use, fusion status, revision status, and preoperative outcome score. RESULTS/ANTICIPATED RESULTS: One hundred thirteen (17%) patients reported moderate/severe SD alone, 70 (10%) reported moderate/severe depression alone, and 57 (8%) reported both moderate/severe SD and depression. In independent models, preoperative SD and depression were significantly associated with 12-month outcomes (all p’s<0.05). After accounting for depression, preoperative SD was only associated with disability, while preoperative depression adjusting for SD remained associated with all outcomes (all p’s<0.05). Patients reporting both moderate/severe SD and moderate/severe depression had 12.6 points higher disability (95%CI=7.4 to 17.8) and 1.5 points higher back (95%CI=0.8 to 2.3) and leg pain (95%CI=0.7 to 2.3) compared to patients with no/mild SD and no/mild depression. DISCUSSION/SIGNIFICANCE: Preoperative SD and depression are independent predictors of 12-month disability and pain when considered in isolation. The combination of SD and depression impacts postoperative outcomes considerably. The high-risk group of patients with moderate/severe SD and depression could benefit from targeted treatment strategies.