This study aimed to investigate the mediatory role of emotional control with respect to the control of anger, depression, and anxiety in the relationship between positive orientation and tiredness/fatigue occurring in a group of Polish nursing students during the COVID-19 pandemic. The study included 894 nursing students from six universities in Poland. A diagnostic survey was applied as the research method, and the data were collected using the Fatigue Severity Scale (FSS), the Courtauld Emotional Control Scale (CECS) and the Positive Orientation Scale (SOP). The mean participant age was 20.73 years (SD = 1.81). More than half of the students in the study showed a low level of positive orientation. Correlational analyses revealed a significant negative correlation between positive orientation and tiredness/fatigue experienced by the students participating in the study (r = −0.336; p < 0.001), and correlation between positive orientation and the overall emotional control index (r = −0.317; p < 0.001), and the indices of control of anger (r = −0.154; p < 0.01), depression (r = −0.376; p < 0.001), and anxiety (r = −0.236; p < 0.01). Analysis of the results also revealed the occurrence of significant, positive links between the controlled emotions and their components and the tiredness/fatigue experienced by nursing students. It is important to take action associated with the prevention of tiredness/fatigue among students and to reinforce a positive orientation and the capacity to control emotions to effectively minimize the effects of the COVID-19 pandemic on nursing students.