Artificial intelligence and machine learning applications are emerging as transformative technologies in medicine. With greater access to a diverse range of big datasets, researchers are turning to these powerful techniques for data analysis. Machine learning can reveal patterns and interactions between variables in large and complex datasets more accurately and efficiently than traditional statistical methods. Machine learning approaches open new possibilities for studying SLE, a multifactorial, highly heterogeneous and complex disease. Here, we discuss how machine learning methods are rapidly being integrated into the field of SLE research. Recent reports have focused on building prediction models and/or identifying novel biomarkers using both supervised and unsupervised techniques for understanding disease pathogenesis, early diagnosis and prognosis of disease. In this review, we will provide an overview of machine learning techniques to discuss current gaps, challenges and opportunities for SLE studies. External validation of most prediction models is still needed before clinical adoption. Utilisation of deep learning models, access to alternative sources of health data and increased awareness of the ethics, governance and regulations surrounding the use of artificial intelligence in medicine will help propel this exciting field forward.