Joint decision-making processes such as negotiations play a vital role in diverse societal contexts spanning from business and politics to sustainability-related negotiations. One of the most prominent examples of how negotiations play an important role in overcoming societal challenges was the COVID-19 vaccine supply negotiations. These negotiations have put the spotlight on an aspect of joint decision-making that always has been of great interest to both negotiation researchers and practitioners yet remains empirically understudied—the effect of uncertainty. In the present article, we develop a framework of uncertainty in negotiation using the COVID-19 vaccine supply negotiations between the European Union and pharmaceutical companies as an example. More specifically, we categorize different kinds of uncertainty based both on mathematical considerations (i.e., differentiation between risk, ambiguity, and uncertainty) as well as on more circumstantial factors. To do so, we adapted the nine kinds of uncertainty in environmental governance proposed by Dewulf and Biesbroek to the more general context of negotiations. We first differentiate between three natures of uncertainty (i.e., lack of knowledge, unpredictability, and interpretations) and three objects of uncertainty (i.e., issue-based, strategy-based, and context-based). Second, we illustrate the psychological barriers that negotiators face when handling uncertainty, before concluding with proposals for practitioners on how to manage different kinds of uncertainty. Overall, we aim at stimulating investigations of the effects of uncertainty in mixed-motive decision-making while simultaneously helping negotiation teachers and practitioners better cope with the additional demands created by specific kinds of uncertainty.