Background: Mindfulness meditation (MM) is often readily applied in university settings as a practical means to reduce stress associated with academic and environmental uncertainties. Little is known, however, about the ideal prescribed frequency and duration of an MM practice to cultivate safe uncertainty when anticipating a stressful task. Purpose: This study therefore examined the effectiveness of a single 25-minute MM in reducing stress compared to concentrative meditation (CM). Methods: The presence of prolonged stress anticipation (A) varied across conditions. Participants (N = 116) were randomly assigned to one of the four groups: MM-A, CM-A, MM, or CM. Both self-reported and physiological stress, assessed by a total distress measure, blood pressure (BP) readings, and heart rate (HR) readings, were recorded pre and post meditation. Results: Parametric analyses demonstrated that all conditions significantly reduced self-reported stress, but not BP and HR levels. Between group differences emerged on one self-reported distress subscale. Discussion: The implications of one-session MM's ability to reduce self-reported stress, but not physiological stress responses, are explored. Translation to Health Education Practice: Health education approaches may benefit from creating implementation monitoring systems when evaluating the impact of brief meditations and similar interventions.