Animals will halt foraging efforts and engage defensive behaviors in response to predator cues. Some researchers have proposed that the switch from appetitive to avoidance behavior resembles anxiety, but most work on this has been performed in a limited number of animal models, primarily zebrafish and rodents. We used adult South African clawed frogs (Xenopus laevis) to determine if the canonical anxiolytic fluoxetine alters predator-induced changes in appetitive and avoidance behavior in a laboratory-based trade-off task that mimics foraging/predator avoidance tradeoffs in the wild. We hypothesized that sub-chronic fluoxetine treatment (20 d) would not affect baseline behavior but would reverse predator-induced changes in food intake, appetitive and avoidance behavior, and the abundance of anxiety related gene transcripts in the optic tectum, a brain area central to ecological decision making in frogs. We found that fluoxetine significantly reduced baseline locomotion compared to vehicle-treated animals. Fluoxetine had no effect on appetitive and avoidance behaviors that were sensitive to predator cues in this assay and did not alter any of the anxiety-related transcripts in the tectum. We conclude that while peripheral sub-chronic administration of fluoxetine significantly reduces locomotion, it does not modify predator-induced changes in approach and avoidance behaviors in this assay. Our findings are not consistent with visual predator cues causing state anxiety in adult frogs.