The current study investigated the independent and combined effects of caffeine and taurine on anxiety-like behavior and neuroendocrine responses in adult zebrafish (Danio rerio). Caffeine (1,3,7-trimethylpurine-2,6-dione), the world’s most commonly used psychoactive drug, acts as an adenosine receptor blocker and a mild central nervous system stimulant. However, excessive use of caffeine is associated with heightened anxiety levels. Taurine (2-aminoethanesulfonic acid), a semi-essential amino acid synthesized within the human brain, has been hypothesized to play a role in regulating anxiolytic behavior. Caffeine and taurine are two common additives in energy drinks and are often found in high concentrations in these beverages. However, few studies have investigated the interaction of these two chemicals with regards to anxiety measures. A suitable vertebrate to examine anxiety-like behavior and physiological stress responses is the zebrafish, which has shown promise due to substantial physiological and genetic homology with humans. Anxiety-like behavior in zebrafish can be determined by analyzing habituation to novelty when fish are placed into a novel tank and scototaxis (light avoidance) behavior in the light-dark test. Stress-related neuroendocrine responses can be measured in zebrafish by analyzing whole-body cortisol levels. The goal of this study was to determine if exposure to caffeine, taurine, or a combination of the two compounds altered anxiety-like behavior and whole-body cortisol levels in zebrafish relative to control. Zebrafish were individually exposed to either caffeine (100 mg/L), taurine (400 mg/L), or both for 15 min. Zebrafish in the control group were handled in the same manner but were only exposed to system tank water. After treatment, fish were transferred to the novel tank test or the light-dark test. Behavior was tracked for the first 6 min in the novel tank and 15 min in the light-tark test. Fifteen min after introduction to the behavioral task, fish were euthanized for the analysis of whole-body cortisol levels. The results demonstrate that caffeine treatment decreased the amount of exploration in the top of the novel tank and increased scototaxis behavior in the light-dark test, which supports the established anxiogenic effect of acute exposure to caffeine. Taurine alone did not alter basal levels of anxiety-like behavioral responses nor ameliorated the anxiogenic effects of caffeine on behavior when the two compounds were administered concurrently. None of the drug treatments altered basal levels of whole-body cortisol. The current results of this study suggest that, at least at this dose and time of exposure, taurine does not mitigate the anxiety-producing effects of caffeine when administered in combination, such as with energy drink consumption.