This pilot randomized controlled trial with economically disadvantaged preschoolers investigated the feasibility and preliminary effects of a mindfulness intervention. We examined its effect on children’s empathy and self-regulation and explored how the curriculum might meet the needs of children attending federally subsidized preschools. Children in five preschool classrooms were randomly assigned by classroom to either a 12-week mindfulness intervention (two classrooms; n = 15) or a treatment as usual (TAU; three classrooms; n = 14) and assessed at three time points: pre-intervention (Time 1), immediately post-intervention (Time 2), and 3-month follow-up (Time 3). Children in the mindfulness intervention significantly increased their attentional focus from Time 1 to Time 2 compared to children in the TAU group. Similarly, compared to the TAU group, children in the mindfulness intervention significantly increased their self-regulation skills at Time 2, and these results were maintained at Time 3. There were no changes in empathy or compassion in either the TAU or mindfulness intervention group. Qualitative analysis of classroom observations and instructor interview data suggested that the intervention can be developmentally structured to meet the needs of economically disadvantaged children.