ABSTRACT: COVID-19 has prompted widespread self-isolation and citywide/countrywide lockdowns. The World Health Organisation (WHO) has encouraged increased digital social activities such as video game play to counteract social isolation during the pandemic. However, there is active debate about the potential for video game overuse, and some video games contain randomised purchases (loot boxes) that may psychologically approximate gambling. In this pre-registered study, we examined the effects of self-isolation and quarantine on excessive gaming and loot box spending. We recruited 1,144 (619 male, 499 female, 26 other) Australian, Aotearoa New Zealand, and US residents who self reported being quarantined or self-isolating (n = 447) or not (n = 619) during the COVID-19 pandemic to a cross-sectional natural experiment. We compared the associations between problem gambling symptomology, excessive gaming and loot box spending for isolated and non-isolated participants. Participants completed the Kessler-10 Psychological Distress Scale, Problem Gambling Severity Index, Internet Gaming Disorder Checklist, a measure of risky engagement with loot boxes, concern about contamination, and reported money spent on loot boxes in the past month, as well as whether they were quarantined or under self-isolation during the pandemic. Although, in our data, excessive gaming and loot box spending were not higher for isolated (self-isolated/ quarantined) compared to non-isolated gamers, the established association between problem gambling symptomology and loot box spending was stronger among isolated gamers than those not isolated. Concerns about being contaminated by germs was also significantly associated with greater excessive gaming and, to a lesser extent, loot box spending irrespective of isolation status. Gamers might be managing concerns about the pandemic with greater video game use, and more problem gamblers may be purchasing loot boxes during the pandemic. It is unclear whether these relationships may represent temporary coping mechanisms which abate when COVID-19 ends. Re-examination as the pandemic subsides may be required. More generally, the results suggest that social isolation during the pandemic may inflate the effect size of some media psychology and gaming effects. We urge caution not to generalise psychological findings from research conducted during the COVID-19 pandemic to be necessarily representative of the magnitude of relationships when not in a pandemic.