Abstract Issue Any effective response to an infodemic, requires prioritizing public health response on identified narrative themes that pose highest risk to health and well-being of populations. High-risk narratives often require more swift and far-reaching action and low-risk narratives require little or no response. Description of the problem Different countries are assigned different levels of risk to specific narratives or concerns, recognizing that for some issues there may be a large gap between the true public health threat and what is generating lots of conversations, concerns and press coverage that indicate a high degree of risk perception that may be unwarranted. WHO developed a risk matrix to apply to global analysis of questions, concerns and narratives about mpox, which resulted in biweekly infodemic intelligence reports that risk-assessed identified infodemic themes and corresponding recommendations for action. Results Risk assessment criteria were defined in the context of WHO’s global infodemic insights analysis for low, medium and high risk and positive sentiment in mpox global outbreak context before conducting the integrated analysis so that insights were reproducible and infodemic response actions were prioritized. This implemented the WHO/UNICEF training manual on 6 steps to produce an infodemic insights report, which includes tools on how to develop and apply a risk matrix for a specific public health question of concern and apply it in analysis. Lessons The approach resulted in rapid, systematic, reproducible and evidence-driven decision-making to respond to the infodemic accompanying the mpox global outbreak. Risk matrices must be adapted to the context of the public health event and the mandate of the health authority taking action. An mpox risk matrix for narratives included adaptation to reflect high-risk from stigmatizing narratives, as well as narratives circulating around or within LGBTQI+ communities. Key messages • A risk matrix must be developed and adapted to the context of each health emergency and level of health authority action. • Prioritization for rapid infodemic response based on a risk assessment is that it facilitates more effective response in a health emergency.