Home confinement during the COVID-19 outbreak had psychological effects that continue to be explored by researchers. This study investigated factors influencing the mental health of mothers caring for special needs children in Italy's first lockdown. Specifically, we investigated the relationships between emotional states of depression, anxiety, stress, perceived distress related to home confinement, coping strategies, and other contextual variables (such as opportunities for distance learning and remote working) in a group of 68 mothers of children with special needs and 68 matched mothers of typically developing children. Data from an online survey showed no significant difference between the two groups. However, the research revealed that being a remote worker was a significant predictor of reduced stress in mothers of children with special needs, while distance learning was a significant predictor of reduced stress in mothers of typically developing children. In addition, the study found that hyperarousal symptoms were predictive of stress in mothers of children with special needs, while intrusive thoughts and avoidance coping were predictive of stress in mothers of typically developing children. In conclusion, further research is needed to develop effective support and intervention strategies for families with children with special needs and to deeply investigate the impact of flexible work arrangements and social aid on the mental health of mothers in non-emergency settings.