2017 Baars, Wijnia and Paas. Self-regulated learning (SRL) skills are essential for learning during school years, particularly in complex problem-solving domains, such as biology and math. Although a lot of studies have focused on the cognitive resources that are needed for learning to solve problems in a self-regulated way, affective and motivational resources have received much less research attention. The current study investigated the relation between affect (i.e., Positive Affect and Negative Affect Scale), motivation (i.e., autonomous and controlled motivation), mental effort, SRL skills, and problem-solving performance when learning to solve biology problems in a self-regulated online learning environment. In the learning phase, secondary education students studied video-modeling examples of how to solve hereditary problems, solved hereditary problems which they chose themselves from a set of problems with different complexity levels (i.e., five levels). In the posttest, students solved hereditary problems, self-assessed their performance, and chose a next problem from the set of problems but did not solve these problems. The results from this study showed that negative affect, inaccurate self-assessments during the posttest, and higher perceptions of mental effort during the posttest were negatively associated with problem-solving performance after learning in a self-regulated way.