PurposeHyperspectral imaging has the potential to improve intraoperative decision making if tissue characterisation is performed in real-time and with high-resolution. Hyperspectral snapshot mosaic sensors offer a promising approach due to their fast acquisition speed and compact size. However, a demosaicking algorithm is required to fully recover the spatial and spectral information of the snapshot images. Most state-of-the-art demosaicking algorithms require ground-truth training data with paired snapshot and high-resolution hyperspectral images, but such imagery pairs with the exact same scene are physically impossible to acquire in intraoperative settings. In this work, we present a fully unsupervised hyperspectral image demosaicking algorithm which only requires exemplar snapshot images for training purposes.MethodsWe regard hyperspectral demosaicking as an ill-posed linear inverse problem which we solve using a deep neural network. We take advantage of the spectral correlation occurring in natural scenes to design a novel inter spectral band regularisation term based on spatial gradient consistency. By combining our proposed term with standard regularisation techniques and exploiting a standard data fidelity term, we obtain an unsupervised loss function for training deep neural networks, which allows us to achieve real-time hyperspectral image demosaicking.ResultsQuantitative results on hyperspetral image datasets show that our unsupervised demosaicking approach can achieve similar performance to its supervised counter-part, and significantly outperform linear demosaicking. A qualitative user study on real snapshot hyperspectral surgical images confirms the results from the quantitative analysis.ConclusionOur results suggest that the proposed unsupervised algorithm can achieve promising hyperspectral demosaicking in real-time thus advancing the suitability of the modality for intraoperative use.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11548-023-02865-7.