Background Simulation-based training’s impact on learning outcomes may be related to cognitive load or emotions during training. We evaluated the association of validated measures of cognitive load and emotion with learning outcomes in simulation-based obstetric internal medicine cases. Methods All internal medicine learners (n = 15) who completed the knowledge test pre-training, post-training (knowledge acquisition), and at 3–6 months (knowledge retention) for all three simulation cases were included. Results Mean knowledge scores differed over time in all three cases (P < 0.0001 for all). Knowledge retention scores were significantly higher only for cases 1 and 3. Cognitive load associated with frustration was positively associated with knowledge acquisition for case 2 (beta = 5.18, P = 0.007), while excitement was negatively associated with knowledge retention in case 1 (beta = –33.07, P = 0.04). Conclusion Simulation-based education for obstetric internal medicine can be effective in select cases. Attention to cognitive load and emotion may optimize learning outcomes.