Single mothers of children with autism spectrum disorders are rarely studied, yet they may experience unique stressors. Researchers asked 122 single mothers to complete questionnaires concerning respite care, daily hassles/uplifts, depression, and caregiver burden. More than half (59.8%) accessed respite care, which was provided for 1h per day, often by multiple sources (41%), such as grandparents and community agencies; most were satisfied with this care. Most mothers (77%) were at risk for clinical depression. While uplifts were negatively correlated with depression, hassles and caregiver burden were positively correlated with depression. Respite care was positively related to daily uplifts, and uplifts mediated the relationship between respite care and depression. Recommendations for researchers, policymakers, and school personnel are offered.