Background: Many parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent wellbeing with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs). Methods: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration's Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643. Findings: We identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0¢30,95%CI -0¢50;-0¢09, p<0¢004, I 2 =46%), specifically NICU-related stress (n = 573, SMD-0¢42,95%CI -0¢61;-0¢23, p<0¢0001, I 2 =0%). In majority of studies higher levels of empowerment, family-centred care, and satisfaction was present with SFRs. No differences were found for anxiety, parent-infant bonding, or self-efficacy. Depression was high (up to 29%) but not different between settings. No studies described post-traumatic stress. Interpretation: Single family rooms seem to facilitate parental presence, involvement, skin-to-skin care, and reduce NICU-related parental stress.