BACKGROUND: Schizophrenia is a rare but devastating condition, affecting about 1% of the world's population and resulting in about 2% of the US health care expenditure. Major impediments to appropriate and timely care include misconceptions, high levels of stigma, and lack of public awareness. Facebook offers novel opportunities to understand public awareness and information access related to schizophrenia, and thus can complement survey-based approaches to assessing awareness that are limited in scale, robustness, and temporal and demographic granularity. OBJECTIVE: The aims of this study were to (1) construct an index that measured the awareness of different demographic groups around schizophrenia-related information on Facebook; (2) study how this index differed across demographic groups and how it correlated with complementary Web-based (Google Trends) and non-Web-based variables about population well-being (mental health indicators and infrastructure), and (3) examine the relationship of Facebook derived schizophrenia index with other types of online activity as well as offline health and mental health outcomes and indicators. METHODS: Data from Facebook's advertising platform was programmatically collected to compute the proportion of users in a target demographic group with an interest related to schizophrenia. On consultation with a clinical expert, several topics were combined to obtain a single index measuring schizophrenia awareness. This index was then analyzed for differences across US states, gender, age, ethnic affinity, and education level. A statistical approach was developed to model a group's awareness index based on the group's characteristics. RESULTS: Overall, 1.03% of Facebook users in the United States have a schizophrenia-related interest. The schizophrenia awareness index (SAI) is higher for females than for males (1.06 vs 0.97, P<.001), and it is highest for the people who are aged 25-44 years (1.35 vs 1.03 for all ages, P<.001). The awareness index drops for higher education levels (0.68 for MA or PhD vs 1.92 for no high school degree, P<.001), and Hispanics have the highest level of interest (1.57 vs 1.03 for all ethnic affinities, P<.001). A regression model fit to predict a group's interest level achieves an adjusted R=0.55. We also observe a positive association between our SAI and mental health services (or institutions) per 100,000 residents in a US state (Pearson r=.238, P<.001), but a negative association with the state-level human development index (HDI) in United States (Pearson r=-.145, P<.001) and state-level volume of mental health issues in United States (Pearson r=-.145, P<.001). CONCLUSIONS: Facebook's advertising platform can be used to construct a plausible index of population-scale schizophrenia awareness. However, only estimates of awareness can be obtained, and the index provides no information on the quality of the information users receive online.