Interactions with parents form the basis of infants’ social-emotional development. Co- regulation during interactions occurs when partners adjust behaviour based on cues from each other. Research has examined co-regulation in low-risk populations, however co-regulation in the context of dyads’ relationships in at-risk populations has yet to be explored. The present study investigated co-regulation and quality of relationships between mothers and their 6-month- old full-term (n = 43) and very low birthweight/preterm (VLBW/preterm; n = 44) infants. The objectives were to examine: (1) how co-regulation changed following a perturbed interaction, (2) how co-regulation differed between full-term and VLBW/preterm infant-mother dyads, and (3) the association between co-regulation and the quality of the mother-infant relationship. Mother-infant interactions were coded for time spent in patterns of co-regulation using the Revised Relational Coding System (Fogel et al., 2003). Quality of the mother-infant relationship was assessed using the Emotional Availability Scales examining maternal and infant dimensions (Biringen et al., 2014; Carter, Little, & Garrity, 1998). Dyads participated in the Still-Face (SF) procedure (Tronick et al., 1978) consisting of two 2-minute face-to-face interactions with a 2-minute period in between where mothers assumed a “still face” and refrained from interacting with their infants. Following the SF period, dyads engaged in more active and disruptive patterns of co-regulation. While full-term dyads engaged in more sequential-symmetrical, VLBW/preterm dyads engaged in more resonant-symmetrical co- regulation. Infant responsiveness, maternal sensitivity, and parental stress were associated with co-regulation. The results highlight the importance of co-regulation and the influence of risk status and relationship quality on co-regulation.