Preterm delivery is a stressful event for mothers, posing them at risk for post-traumatic stress reactions. This study examined the degree of depressive symptoms and post-traumatic stress in mothers of preterm infants born before 32 gestational weeks depending on whether the infant received music therapy in the neonatal intensive care unit (NICU) or not. We included 33 mothers of preterm infants enrolled in a previously described prospective randomized controlled trial, of whom 18 received music therapy (mean mothers’ age 34.1 ± 4.6 years) and 15 did not (mean mothers’ age 29.6 ± 4.2). The degree of depressive symptoms, anxiety and acute stress reactions of these mothers were measured by using the German version of the Center for Epidemiologic Studies Depression Scale (CES-D) and Impact of Events Scale-Revised (IES-R) one week after birth (T1) and at infants’ hospital discharge (T2). 605 music therapy sessions with a mean duration of 24.2 ± 8.6 min (range 10 to 50 min) were conducted two times a week from the second week of life (T1) until discharge (T2) to the infants from the intervention group. The infants from the control group received standard medical care without music therapy. The mean total CES-D score decreased from T1 (mean 34.7, 95% Confidence Interval (CI) 31.1–38.1) until T2 in all mothers (mean 16.3, 95% CI 12.6–20.1). Mothers whose infants received music therapy showed stronger declines of depressive and stress symptoms (with music therapy: CES-D mean difference of total score 25.7, 95% CI 20.0–31.3, IES-R mean difference of total score 1.7, 95% CI 0.9–2.5, IES-R mean difference of subcategory hyperarousal 10.2, 95% CI 6.2–14.3; without music therapy: CES-D mean difference of total score 9.5, 95% CI 3.8–15.3, IES-R mean difference of total score 0.1, 95% CI −1.0–1.2, IES-R mean difference of subcategory hyperarousal 1.6, 95% CI −4.7–7.9). Effect sizes were strong for CES-D, IES-R, and the hyperarousal subcategory, moderate for intrusion, and low for avoidance. These findings show that mothers of preterm infants are highly susceptible to supportive non-medical interventions such as music therapy to reduce psychological symptoms and distress during their infants’ NICU stay.