Stress-related problems are increasing among Swedish adolescents, especially among females. The aims of this study were to survey the incidence of stress symptoms among 16-year-olds, to investigate the related gender differences, and to understand the factors that may contribute to stress symptoms. The study is questionnaire based, and the sample included 304 first-year high school students from two comparable schools. More than 30% of the high school students reported serious stress symptoms. Almost every second girl and every fifth boy reported that they felt stressed to a high degree. 8.2% were found to have severe stress symptoms, which would be considered a sign of chronic stress in adults. Besides the perception of high demands, low levels of global self-esteem, sleep disturbances, and poor social support played a crucial role in the prediction of stress symptoms. The findings highlight the need to develop and implement adequate stress prevention measures for adolescents.