The study examined the effects of two different instructional interventions as support for scientific discovery learning using computer simulations. In two well-known categories of difficulty, data interpretation and self-regulation, instructional interventions for learning with computer simulations on the topic "ecosystem water" were developed and tested using a sample of 124 eighth graders in science classes. The results demonstrate the effectiveness of instructional support for domain-specific factual, conceptual, and procedural knowledge acquisition. Students who received either only instructional support for data interpretation or only for self-regulation achieved the highest learning outcomes. However, a combination of instructional support for data interpretation and self-regulation seemed detrimental for knowledge acquisition. Students who received instructional interventions for both data interpretation and self-regulation also showed the highest values of perceived cognitive load. High cognitive load could be a reason for why a combination of particular instructional interventions does not lead to the expected positive learning outcomes.