The work and family interface elicits work–family conflict (WFC) leading to positive and negative outcomes. Sex is a central element in WFC, with a wealth of studies reporting either sex differences or similarities. The presence of children at home, however, is a rather understudied moderator. This study aimed to contrast whether two main components of WFC, work interference with family (WIF) and family interference with work (FIW) associated differentially with wellbeing and strain depending on sex or children. There were data from 762 Spanish individuals (455 females) in dual-earner families. A structural equation model with four latent variables (WIF, FIW, wellbeing and strain) was contrasted across two moderators, sex and children. Males and females endured a similar association between WIF and FIW with wellbeing and strain compared with workers with children. Childless workers experienced lower associations between FIW with wellbeing and strain compared with workers with children. Children at home rather than sex alone elicit stronger links of WFC with wellbeing and strain. Examining the presence of children at home, including children ages, should be conducted regularly in WFC research.