Objective: To analyse the association between social inequalities and the leprosy burden in a low endemicity scenario in the state of São Paulo, Brazil. Methods: This ecological study was carried out in the city of Ribeirão Preto, state of São Paulo, Brazil, considering leprosy cases notified from 2006 to 2016. Regarding social inequalities, dimensions related to high household density, literacy, home occupation conditions, health conditions, household income, ethnicity and age were considered. The generalised additive model for location, scale and shape (GAMLSS) was used to verify the association between the social inequalities and leprosy burden. Results: The increase in men and women with no education and people with an income of 1 to 2 minimum wages was associated with a relative increase in the number of leprosy cases (7.37%, 7.10% and 2.44%, respectively). Regarding the ethnicity variables, the increase in the proportion of men (black) and women (mixed race) with no schooling was associated with a relative increase in the number of cases of the disease (10.77% and 4.02%, respectively). Finally, for people of mixed race or ethnicity, the increase in the proportion of households with 1/2 to 1 minimum wage was related to a relative decrease in the total number of cases (-4.90%). Conclusion: The results show that the determinants associated with the increase in leprosy cases are similar to those in Brazilian hyperendemic regions, and that even in cities with low endemicity, social inequality is one of the main determinants of the disease.