Purpose: We conducted this case-control study to determine the role of 2 neuropsychologic variables (sleep and depression) as possible risk indicators for the development of temporomandibular disorders (TMD). Materials and Methods: Neuropsychologic tests, traditional signs and symptoms of TMD, and social and economic variables were analyzed. Seventy-two predominantly muscle-related TMD patients (Research Diagnostic Criteria for TMD groups Ia, Ib, and IIIa) and 30 age- and sex-matched pain-free controls were included in the population. Results: Overall, TMD patients had statistically significantly higher sleep and depression scores on the Sleep Assessment Questionnaire and on the Brazilian Portuguese version of the Beck Depression Inventory, with odds ratios of 5 and 1.6, respectively. These results remained unchanged even after controlling for 8 confounders in the logistic regression analysis. Spontaneous pain and pain on palpation (grade 2 or higher) were also statistically significantly worse in TMD patients. In the forward-step logistic regression analysis, we also found that the combination of our best TMD predictors (ie, sleep, cigarettes, alcohol) had a better predictive value (percent agreement = 78.69%) than when the variables were analyzed alone. Conclusion: Sleep and depression are considered important risk indicators for the development of TMD.