Importance The COVID-19 pandemic impacted healthcare beyond COVID-19 infections. A better understanding of how COVID-19 worsened the opioid crisis has potential to inform future response efforts. Objective To summarize changes from the COVID-19 pandemic on outcomes regarding opioid use and misuse in the USA and Canada. Evidence review We searched MEDLINE via PubMed, EMBASE, and CENTRAL for peer-reviewed articles published between March 2020 and December 2021 that examined outcomes relevant to patients with opioid use, misuse, and opioid use disorder by comparing the period before vs after COVID-19 onset in the USA and Canada. Two reviewers independently screened studies, extracted data, assessed methodological quality and bias via Newcastle-Ottawa Scale, and synthesized results. Findings Among 20 included studies, 13 (65%) analyzed service utilization, 6 (30%) analyzed urine drug testing results, and 2 (10%) analyzed naloxone dispensation. Opioid-related emergency medicine utilization increased in most studies (85%, 11/13) for both service calls (17% to 61%) and emergency department visits (42% to 122%). Urine drug testing positivity results increased in all studies (100%, 6/6) for fentanyl (34% to 138%), most (80%, 4/5) studies for heroin (-12% to 62%), and most (75%, 3/4) studies for oxycodone (0% to 44%). Naloxone dispensation was unchanged and decreased in one study each. Interpretation Significant increases in surrogate measures of the opioid crisis coincided with the onset of COVID-19. These findings serve as a call to action to redouble prevention, treatment, and harm reduction efforts for the opioid crisis as the pandemic evolves. PROSPERO registration number CRD42021236464.