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The way media portray public health problems influences the public’s perception of problems and related solutions. Social media allows users to engage with news and to collectively construct meaning. This paper examined news in comparison to user-generated content related to opioids to understand the role of second-level agenda-setting in public health. We analyzed 162,760 tweets about the opioid crisis, and compared the main topics and their sentiments with 2998 opioid stories from The New York Times online. Evidence from this study suggests that second-level agenda setting on social media is different from the news; public communication about opioids on X/Twitter highlights attributes that are different from those highlighted in the news. The findings suggest that public health communication should strategically utilize social media data, including obtaining consumer insight from personal tweets, listening to diverse views and warning signs from issue tweets, and tuning in to the media for policy trends.