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Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or overexpression of a misfolded mutant secretory protein. Neither pretreatment with nor delayed addition of TUDCA conferred protection against Tm. Importantly, attenuation of Tm-induced toxicity required TUDCA's critical micelle forming concentration, suggesting a mechanism where TUDCA directly sequesters drugs. Indeed, in several assays, TUDCA-treated cells closely resembled cells treated with lower doses of Tm. In addition, we found TUDCA can inhibit dyes from labeling intracellular compartments. 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