The study aimed to assess the perception of a higher risk of COVID-19 infection among young people who used e-cigarettes, and its association with a change in the use of e-cigarettes during the pandemic in Nigeria. A secondary analysis of the Nigerian component of a multi-country online survey data, which was obtained from adolescents and young adults on e-cigarette use from November 1st to December 30th, 2021, was conducted. Multi-nominal regression analyses were done to determine the associations between the dependent (use of e-cigarettes) and independent (perception that e-cigarette users are more likely to be infected with COVID-19) variables after adjusting for confounders (health status, COVID-19 status, HIV status, anxiety level, age and sex). Of the 568 respondents (52.8% male), 122 (21.5%) perceived that e-cigarette users were more likely to be infected with COVID-19. In addition, 188 (33.1%) respondents increased e-cigarette smoking during the pandemic. A greater percentage of participants who perceived that e-cigarette use is associated with a greater risk of COVID-19 infection, and a significantly higher percentage of participants with high levels of anxiety reported decreased e-cigarette use (28.6% versus 13.3%, p = 0.029). The perception that e-cigarette use increased the risk for COVID-19 was associated with higher odds of an increase in e-cigarette use (AOR: 1.328) and lower odds of a decrease in e-cigarette use (AOR: 0.580) during the COVID-19 pandemic, though these associations were not statistically significant. The persistence of e-cigarette use among the youth in Nigeria despite awareness of COVID-19 risks highlights the need for stronger public health interventions. Simply providing information on risks is insufficient; targeted strategies addressing addiction, social factors, and accessibility are crucial for meaningful behavioural change.