The detrimental effect of ocean acidification (OA) on marine animals with carbonate exoskeletons or shells is an issue drawing increased attention in marine biology and ecology, yet few studies have focused on the impact on gelatinous organisms like scyphozoan medusae. Here, we examined the physiological tolerance of Cassiopea sp., an abundant genus of scyphozoans valuable for their role as bioindicators and for having similarities to other cnidarians, to OA by conducting three, 12-week trials using CO2 diffusers and electronic pH controllers to incrementally lower the water to test pHs of 7.5 and 7.0. The impact of reduced pH on the survival, pulse rate, bell diameter, and reorientation and settlement abilities of Cassiopea sp. medusae were measured weekly. Cassiopea sp. was tolerant to pH 7.5 while further reduction of the pH to 7.0 resulted in 22.22% mortality rate, which was significantly different from the control and treatment pH 7.5. Significant differences between the treatment pH 7.0 and control first occurred on day 23.5 with a 50% reduction in the pulse rate, and on day 36 with a 16.6% reduction in bell diameter, while pH 7.5 had no effect. By the final time point of 66 days in treatment pH 7.0, there was an 87% reduction in pulse rate and a 36% reduction in bell diameter versus control. Reduced pH 7.0 caused bell malformations, inhibited swimming abilities, and deterioration of the oral arm feeding apparatus, but had no effect on the orientation and settlement assay. Observations indicate that asexual reproduction via planuloid production and strobilation was unaffected by pH reduction, though polyps in treatment pH 7.0 gave rise to ephyrae with inverted bells. Combined, findings from this study demonstrate Cassiopea sp. to be resilient to the end of century ocean acidity prediction of pH 7.6, and vulnerable to more severe OA to pH 7.0.