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News media plays a large role in the information the public receives during an infectious disease outbreak, and may influence public knowledge and perceptions of risk. This study analyzed and described the content of U.S. news media coverage of Zika virus and Zika response during 2016. A random selection of 800 Zika-related news stories from 25 print and television news sources was analyzed. The study examined 24 different messages that appeared in news media articles and characterized them using theories of risk perception as messages with characteristics that could increase perception of risk (risk-elevating messages; n = 14), messages that could decrease perception of risk (risk-minimizing messages; n = 8), or messages about travel or testing guidance (n = 2). Overall, 96% of news stories in the study sample contained at least one or more risk-elevating message(s) and 61% contained risk-minimizing message(s). The frequency of many messages changed after local transmission was confirmed in Florida, and differed between sources in locations with or without local transmission in 2016. Forty percent of news stories included messages about negative potential outcomes of Zika virus infection without mentioning ways to reduce risk. Findings from this study may help inform current federal, state, and local Zika responses by offering a detailed analysis of how news media are covering the outbreak and response activities as well as identifying specific messages appearing more or less frequently than intended. Findings identifying the types of messages that require greater emphasis may also assist public health communicators in responding more effectively to future outbreaks.