In recent years, there has been a rising interest in medical biochemistry in the fish farming industry to cover the need for rapid, non-lethal methods to monitor fish health and support sustainable management practices. Several challenges need to be solved before non-lethal fish blood sampling and analysis can be routinely implemented in fish health care, such as guidelines to how blood sampling from fish can be conducted in a practical way that safeguards fish welfare. Sampling of blood via puncture of the caudal vasculature involves traversing the needle through several tissue structures like the skin, skeletal muscle, and vasculature. Other important structures found in this region are nerves, in particular the truncus sympathicus and the ventral roots exiting from the spinal cord and vertebrae. During sampling, all these structures are vulnerable to damage. In an effort to evaluate this potential harm and other impacts on fish welfare, we conducted a study involving Atlantic salmon in fresh water (50-100 g) and sea water (250-500 g). The salmon were subjected to sampling of different blood volumes in ambient water temperatures of 5, 12, and 15°C. Anaemia and tissue damage were monitored by different methods. The results revealed significant differences in the ability to regenerate between fish sizes and water temperatures. Here we will emphasize the results from the histology, as we consider such analyses a prerequisite for establishing a best practice for non-lethal blood sampling. Some possible injuries, their impact on fish health and potential for regeneration are described.