College students can be sedentary for a majority of the day, which may exacerbate mental health issues or lead to declines in cognitive task performance; however, interventions to address sedentary behaviors may not positively influence everyone. Therefore, the present study sought to identify inter-individual cognitive performance and mood changes of college students during the performance of a cognitive task battery, while seated, standing and with intermittent bouts of walking. Participants (n = 31, age = 25.80 ± 3.61 yrs, 7 male) completed a series of baseline questionnaires including the Trait Mental and Physical Energy and Fatigue survey. Using a randomized controlled cross-over design, participants completed 3 separate testing sessions. At each session, they performed a series of three rounds of cognitive tasks for 27 min and self-reporting mood states for 1 min in the seated position. Each round of cognitive testing was followed by a 2 min break. Each testing day had participants spend the 2 min break in a different condition: sitting, standing, or walking. A series of mixed ANOVAs were used for the primary analysis and a combination of machine learning regressors and classifiers were used for the secondary analysis. Our results suggest that there are unique inter-individual responses to each of the interventions used during the 2 min break. Participants who were low-trait mental and low-trait physical energy benefited the most from the standing desk intervention, while also reporting significant benefits of intermittent walking. However, participants who were low-trait mental fatigue had significant negative consequences of using both standing desks and walking intermittently, while those who were high-trait mental fatigue saw no change in cognitive responses or moods in those conditions. Post hoc machine learning analyses had modest accuracy rates (MAEs < 0.7 for regressors and accuracy rates >60% for classifiers), suggesting that trait mental and physical energy and fatigue may predict inter-individual responses to these interventions. Incorporating standing desks into college classroom settings may result in some students receiving cognitive benefits when inter-individual variability in mood and cognitive responses are accounted for.