Labor migration has increased the risk of HIV infection among the wives of labor migrants in Nepal. We conducted a matched case control study to identify the social and behavioral factors for HIV infection among the wives of labor migrants in Nepal. We interviewed 112 wives of labor migrants diagnosed with HIV (cases) and 112 wives of labor migrants testing negative for HIV (controls) and used logistic regression analysis to assess independent factors associated with HIV infection. Literacy status was the only one woman-related social factor associated with HIV infection. Meanwhile literacy status, age when going abroad for the first time and country of migration were the husband-related social factors and alcohol consumption, living alone abroad and having an unpaid partner abroad were the husband-related behavioral factors associated with HIV infection in the wives. Given the husband-related social and behavioral factors are mostly determining the risk of HIV infection in the wives in our study, prevention efforts must incorporate behavior change approaches targeting specifically to labor migrants and also to their wives.