Qualitative research is integral to the pandemic response. Qualitative methods are ideally suited to generating evidence to inform tailored, culturally appropriate approaches to COVID-19, and to meaningfully engaging diverse individuals and communities in response to the pandemic. In this paper, we discuss core ethical and methodological considerations in the design and implementation of qualitative research in the COVID-19 era, and in pivoting to virtual methods—online interviews and focus groups; internet-based archival research and netnography, including social media; participatory video methods, including photo elicitation and digital storytelling; collaborative autoethnography; and community-based participatory research. We identify, describe, and critically evaluate measures to address core ethical challenges around informed consent, privacy and confidentiality, compensation, online access to research participation, and access to resources during a pandemic. Online methods need not be considered unilaterally riskier than in-person data collection; however, they are clearly not the same as in-person engagement and require thoughtful, reflexive, and deliberative approaches in order to identify and mitigate potential and dynamically evolving risks. Ensuring the ethical conduct of research with marginalized and vulnerable populations is foundational to building evidence and developing culturally competent and structurally informed approaches to promote equity, health, and well-being during and after the pandemic. Our analysis offers methodological, ethical, and practical guidance in the COVID-19 pandemic and considerations for research conducted amid future pandemics and emergency situations.