Mate products are sometimes marketed as "caffeine-free" alternatives to coffee and tea, and said to have fewer negative effects. This is often based on a claim that the primary active xanthine in mate is "mateine", said to be a stereoisomer of caffeine. However, caffeine has no stereoisomers. "Mateine" is regarded as synonymous with caffeine.

Researchers at Florida International University in Miami have found that yerba mate does contain caffeine, but some people seem to tolerate it better than coffee or tea.

From reports of personal experience with mate, its physiological effects are similar to—yet distinct from—more widespread caffeinated beverages like coffee or tea. Users report a mental state of wakefulness, focus and alertness reminiscent of most stimulants, but often remark on mate's unique lack of the negative effects typically created by other such compounds, such as anxiety, diarrhea, "jitteriness," and heart palpitations.

Reasons for mate's unique physiological attributes are beginning to emerge in scientific research. Studies of mate, though very limited, have shown preliminary evidence that the mate xanthine cocktail is different from other plants containing caffeine most significantly in its effects on muscle tissue, as opposed to those on the central nervous system, which are similar to those of other natural stimulants. Mate has been shown to have a relaxing effect on smooth muscle tissue, and a stimulating effect on myocardial (heart) tissue.

Composition of yerba mate