Objective: To compare the level of self-reported perceived global and situational stress, sleep disturbance, and the level of wellness between mothers with an infant in Neonatal Intensive Care Units (NICU) who are categorized as having high or low depressive symptoms.Methods: Cross-sectional comparative design which included 55 first-time mothers who were in their second postpartum week and had a preterm infant admitted to the NICU of three urban hospitals in the southeastern United States. Participants wore wrist actigraphy and completed sleep diary for 2-3 days, in addition to completing self-report questionnaires for depressive symptoms, stress, perceived sleep disturbance, and well-being. Participants were categorized as having high (≥ 13) or low (< 13) depressive symptoms by using the total score of Edinburgh Postnatal Depression Scale.Results: Approximately 62% of the study participants reported high depressive symptoms. Mothers with high depressive symptoms reported greater stress and less well-being compared to those with less depressive symptoms. With the exception of wake after sleep onset, there was no statistically significant difference in the sleep between the two groups; all of the mothers had clinically significant poor sleep. Conclusions:Mothers of infants in the NICU who experienced higher depressive symptoms also reported greater stress and experienced poorer sleep; altogether, this may compromise one's ability to learn and care for a child in the NICU. Nurses and members of the healthcare team should be attuned to signs and symptoms of depression, perhaps incorporating more formal screening of mothers, educational and support resources, and referral systems.