Purpose <p>Daytime sleepiness has increased in young adults. This study aimed to test the hypothesis that isometric exercise training could improve daytime sleepiness in female university students.</p> Methods <p>Twenty-two healthy university female students were assigned to either the control (n = 11) or the training (n = 11) group. The training group performed unilateral isometric handgrip sessions three times per week for 8&#xa0;weeks. The training protocol consisted of four 2-min sets of isometric handgrip exercise at 25% of maximal voluntary contraction, separated by 3-min rest periods. Daytime sleepiness (using the Epworth Sleepiness Scale: ESS), sleep quality (using the Pittsburgh Sleep Quality Index: PSQI), and the resting blood pressure were measured at baseline (0w), week 4 (4w), week 8 (8w), and after 6&#xa0;weeks of detraining period (DeTR-6w).</p> Results <p>Eight responders and three non-responders in resting blood pressure reduction were observed within training group at 8w. A significant group × time interaction was observed in ESS between those responders in training group and control group (<i>p</i> = 0.007). The responders indicated a significant reduction of ESS from 0 to 8w (mean difference, −2.3 score [95% CI, −0.1 to −4.4], <i>p</i> = 0.039), and it remained at that level from 8w to DeTR-6w (mean difference, 0.8 score [95% CI, −1.4 to 2.9], <i>p</i> = 0.80). The PSQI global score was not significant interaction between groups.</p> Conclusions <p>Isometric handgrip training may reduce daytime sleepiness irrespective of sleep quality among hypotensive responders to that training in female university students.</p>