Background People Who Inject Drugs (PWID) are subject to distinct socio-structural inequalities that can expose them to high risks of COVID-19 transmission and related health and social complications. In response to COVID-19 mitigation strategies, these vulnerabilities are being experienced in the context of adapted drug treatment service provision, including reduced in-person support and increased regulatory flexibility in opioid substitution therapy (OST) guidelines. This study aimed to explore the longer-term impact of the pandemic on the health and wellbeing of PWID in the UK, including provider and client experiences of treatment changes. Methods Interviews were conducted with 19 PWID and 17 drug treatment providers between May and September 2021, recruited from drug and homelessness charities providing treatment services and healthcare in the UK. Data were analysed using reflexive thematic analysis. Results Most participants expressed ongoing fears of COVID-19 transmission, although socio-structural inequalities limited the contexts in which physical distancing could be practised. In addition, virus mitigation strategies altered the risk environment for PWID, resulting in ongoing physical (e.g. changing drug use patterns, including transitions to crack cocaine, benzodiazepine and pregabalin use) and socio-economic harms (e.g. limited opportunities for sex work engagement and income generation). Finally, whilst clients reported some favourable experiences from service adaptations prompted by COVID-19, including increased regulatory flexibility in OST guidelines, there was continued scepticism and caution among providers toward sustaining any treatment changes beyond the pandemic period. Conclusions Whilst our findings emphasize the importance of accessible harm reduction measures attending to changing indices of drug-related harm during this period, there is a need for additional structural supports to ensure pre-existing disparities and harms impacting PWID are not exacerbated further by the conditions of the pandemic. In addition, any sustained policy and service delivery adaptations prompted by COVID-19 will require further attention if they are to be acceptable to both service users and providers.