DELiVR is a virtual reality (VR)-trained deep-learning pipeline designed to detect c-Fos+ cells, markers of neuronal activity, in cleared mouse brains. The pipeline leverages VR annotation to generate high-quality reference data, significantly accelerating training data generation and improving segmentation accuracy compared to traditional 2D slice-based methods. DELiVR is packaged in a user-friendly Docker container and a Fiji plugin, making it accessible to biologists without advanced coding skills. The pipeline includes a comprehensive toolkit for data visualization and can be customized for other cell types. DELiVR was applied to investigate cancer-related brain activity, revealing distinct activation patterns in weight-stable cancer compared to cachectic cancer, particularly in areas related to sensory processing and foraging. Overall, DELiVR is a robust tool for analyzing whole-brain imaging data in health and disease, offering a seamless and efficient solution for cell detection and registration to the Allen Brain Atlas.DELiVR is a virtual reality (VR)-trained deep-learning pipeline designed to detect c-Fos+ cells, markers of neuronal activity, in cleared mouse brains. The pipeline leverages VR annotation to generate high-quality reference data, significantly accelerating training data generation and improving segmentation accuracy compared to traditional 2D slice-based methods. DELiVR is packaged in a user-friendly Docker container and a Fiji plugin, making it accessible to biologists without advanced coding skills. The pipeline includes a comprehensive toolkit for data visualization and can be customized for other cell types. DELiVR was applied to investigate cancer-related brain activity, revealing distinct activation patterns in weight-stable cancer compared to cachectic cancer, particularly in areas related to sensory processing and foraging. Overall, DELiVR is a robust tool for analyzing whole-brain imaging data in health and disease, offering a seamless and efficient solution for cell detection and registration to the Allen Brain Atlas.