Objectives: We assessed the influence of the risk of self-medication on health locus of control and the experienced symptoms - physical, psychological, and spiritual in a group of students from urban and rural regions. Methods: This cross-sectional study included a convenience sample of 200 students from urban (N=100) and rural (N=100) areas. We used 3 research tools: Multidimensional Health Locus of Control (MHLC); List of Noo-Psychosomatic Symptoms (LS-NPS); and Self-medication Risk Questionnaire (SMRQ). Results: We found a statistically significant difference between rural and urban residents in the area of the influence of chance (CHLC) on the control of health (p < .05). The correlations between the general assessment of the risk of self-medication and two health locus of control factors were statistically significant (p < .05). A greater tendency to undertake the risk of self-medication is connected to living in the city and prescribing importance in the control of one's health to others or chance. Conclusions: Predictors of the assessment of the risk of self-medication were 2 measures of health locus of control, ie, influence of others and chance and the residence of students.