Background: Heart rate variability (HRV) measures have been shown to be positively associated with cognitive processing, while a positive association between cognitive processing and academic performance has been demonstrated. Objectives: To determine whether resting HRV or HRV marker response to either a cognitive or an orthostatic challenge is significantly associated with a first-year university student’s academic performance. Method: HRV markers used in the study included total power (TP) as a measure of overall HRV and the root mean square of successive differences (RMSSD) as a measure of parasympathetic influence on the heart. Academic performance was determined by standardized general mean scores. Results: Greater supine overall HRV (TP) was significantly associated with greater academic performance predominantly in females. Vagal (RMSSD) measures were not shown to be associated with academic performance. Conclusions: This, to our knowledge, is the first study to show that overall HRV has a significant positive association with academic performance of a first-year university student.