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This paper synthesizes the efforts of an interdisciplinary, University-convened communication task force in the U.S. that used science communication theory to develop an effective strategy during the early stages of the COVID-19 pandemic. We outline recommendations for researchers and practitioners who are, or are interested in, implementing theory-based communication practices while describing how we dealt with the unforeseen realities we faced. Overall, we recommend that effective public health and science communication should be based on theory and formative evaluation while relying on established infrastructure, real-time data, a deep understanding of intended target audiences, and intentional coordination with community partners.