The aim of this study is to investigate the influence of content knowledge on students' socio-scientific argumentation in the Swedish National Assessment in biology, chemistry and physics for 12-year-olds. In Sweden, the assessment of socio-scientific argumentation has been a major part of the National Assessment during three consecutive years and this study utilizes data on student performance to investigate (a) the relationship between tasks primarily addressing argumentation and tasks addressing primarily content knowledge as well as (b) students' performance on argumentation tasks, which differ in relation to content, subject, aspect of argumentation and assessment criteria. Findings suggest a strong and positive relationship between content knowledge and students' performance on argumentation tasks. The analysis also provides some hypotheses about the task difficulty of argumentation tasks that may be pursued in future investigations.