Objective: Myasthenia gravis (MG) is an autoimmune disease leading to fatigable muscle weakness. Extra-ocular and bulbar muscles are most commonly affected. We aimed to investigate whether facial weakness can be quantified automatically and used for diagnosis and disease monitoring. Methods: In this cross-sectional study, we analyzed video recordings of 70 MG patients and 69 healthy controls (HC) with two different methods. Facial weakness was first quantified with facial expression recognition software. Subsequently, a deep learning (DL) computer model was trained for the classification of diagnosis and disease severity using multiple cross-validations on videos of 50 patients and 50 controls. Results were validated using unseen videos of 20 MG patients and 19 HC. Results: Expression of anger (p = 0.026), fear (p = 0.003), and happiness (p < 0.001) was significantly decreased in MG compared to HC. Specific patterns of decreased facial movement were detectable in each emotion. Results of the DL model for diagnosis were as follows: area under the curve (AUC) of the receiver operator curve 0.75 (95% CI 0.65–0.85), sensitivity 0.76, specificity 0.76, and accuracy 76%. For disease severity: AUC 0.75 (95% CI 0.60–0.90), sensitivity 0.93, specificity 0.63, and accuracy 80%. Results of validation, diagnosis: AUC 0.82 (95% CI: 0.67–0.97), sensitivity 1.0, specificity 0.74, and accuracy 87%. For disease severity: AUC 0.88 (95% CI: 0.67–1.0), sensitivity 1.0, specificity 0.86, and accuracy 94%. Interpretation: Patterns of facial weakness can be detected with facial recognition software. Second, this study delivers a ‘proof of concept’ for a DL model that can distinguish MG from HC and classifies disease severity.@en