Abstract Background Manual assessment of bone marrow signal is time-consuming and requires meticulous standardisation to secure adequate precision of findings. Objective We examined the feasibility of using deep learning for automated segmentation of bone marrow signal in children and adolescents. Materials and methods We selected knee images from 95 whole-body MRI examinations of healthy individuals and of children with chronic non-bacterial osteomyelitis, ages 6–18 years, in a longitudinal prospective multi-centre study cohort. Bone marrow signal on T2-weighted Dixon water-only images was divided into three color-coded intensity-levels: 1 = slightly increased; 2 = mildly increased; 3 = moderately to highly increased, up to fluid-like signal. We trained a convolutional neural network on 85 examinations to perform bone marrow segmentation. Four readers manually segmented a test set of 10 examinations and calculated ground truth using simultaneous truth and performance level estimation (STAPLE). We evaluated model and rater performance through Dice similarity coefficient and in consensus. Results Consensus score of model performance showed acceptable results for all but one examination. Model performance and reader agreement had highest scores for level-1 signal (median Dice 0.68) and lowest scores for level-3 signal (median Dice 0.40), particularly in examinations where this signal was sparse. Conclusion It is feasible to develop a deep-learning-based model for automated segmentation of bone marrow signal in children and adolescents. Our model performed poorest for the highest signal intensity in examinations where this signal was sparse. Further improvement requires training on larger and more balanced datasets and validation against ground truth, which should be established by radiologists from several institutions in consensus.