The threat of a United States (U.S.) Zika virus pandemic during 2015-2016 was associated with public anxiety. Such threats represent opportunities to examine hypotheses about health anxiety. The present study investigated psychological predictors of Zika-related anxiety during the 2015-2016 outbreak. U.S. adults (N = 216) completed a battery of measures assessing Zika-related anxiety as well as psychological variables hypothesized to predict anxious responding to the threat of a domestic Zika outbreak. Contrary to hypotheses, regression analyses indicated that only contamination severity overestimates and greater Zika knowledge significantly predicted Zika-related anxiety. Study limitations and clinical implications are discussed.