Background: The first national COVID-19 lockdown in the United Kingdom between March to July 2020 resulted in sudden and unprecedented disruptions to daily life. This study sought to understand the impact of COVID-19 non-pharmaceutical interventions (NPIs), such as social distancing and quarantine, on people’s lived experiences, focusing on social connections and relationships. Methods: Data were generated through 20 in-depth online and telephone interviews, conducted between May and July 2020, and analysed using thematic analysis informed by an ecological framework. Results: Findings show that the use of NPIs impacted social relationships and sociality at every level, disrupting participant’s sense of self; relationships with their partners, household members, neighbours, and communities; and polarising social and political views. However, experiences of personal meaning-making and reflection, and greater social connectedness, solidarity, and compassion – despite physical distance – were also common. Conclusions: Participant’s lived experiences of the first UK lockdown underscore the interconnectedness of relationships at the individual, community and societal level and point towards the important role of trust, social cohesion, and connectedness in coping with pandemic stress and adversity. Where infectious disease prevention measures rupture sociality, support for social connection at every relational level is likely to help build resilience in light of ongoing COVID-19 restrictions.