Ocean pH is decreasing due to anthropogenic activities, and the consequences of this acidification on marine fauna and ecosystems are the subject of an increasing number of studies. Yet, the impact of ocean acidification (OA) on several abundant and ecologically important taxa, such as medusozoans, is poorly documented. To date there have been no studies on the effect of post-2050 OA projections on the medusa stage of jellyfish. As medusae represent the reproductive stage of cnidarians, negative impacts on adult jellyfish could severely impact the long-term survival of this group. Using a laboratory experiment, we investigated the effect of 2300 OA projections (i.e. pH of 7.5) on the mortality rate of the medusa-stage of the cubozoan species Carybdea xaymacana, compared to ambient seawater pH conditions (i.e. pH of 8.1). After a 12-h exposure to OA, C. xaymacana medusae suffered higher mortality rates compared to ambient conditions. This study represents the first evidence of the potential lethal effects of post-2050 OA projections on jellyfish. The higher metabolic rates of cubozoans compared to other cnidarians might make box jellyfish more vulnerable to OA. A decrease in the density of cnidarians could lead to harmful ecological events, such as algal blooms.