There is a lack of studies on the level of stress and health of families of workers in road transport. This study aimed to evaluate the perceived stress level and Family Effectiveness of family members of road transport workers. A quantitative study was carried out with family members of road transport workers in the southern region of Brazil. For the data collection, a sociodemographic form, the Perceived Stress Scale (PSS), and the Evaluation of Family Effectiveness Strategies were used. The data were analyzed by simple frequency, Spearman correlation coefficient (ρ) (p < 0.05), and descriptive analysis from the perspective of the Systemic Organization. 49 family members of road transport workers were participants. Perceived stress was higher in family members who had more than nine years of schooling, the targets of Control and Growth were higher in the evaluation of Family Effectiveness. The Control target was also higher in families with more than three people. The Coherence dimension had higher levels in families with health problems and whose income was less than $792.00 US dollars per month. In the Individuation dimension, income over $792.00 had better results. The Maintenance dimension of the system was higher in families whose drivers’ activity was as an intercity driver, as well as in the Stability target. In conclusion, the social factors such as schooling, income, diseases, type of worker activity in road transport, and number of people in the family influenced perceived stress and Family Effectiveness, which demonstrates the need to increase the promotion of health care of the families of road transport workers.