Advanced NMR measurements of biological samples may take several hours. Preanalytical issues may impact the metabolite content, potentially leading to misinterpretation. Our aim was to investigate by 1H HR-MAS NMR the impact of different cell handling preparation protocols (lysis with and without heating) on the stability of the cell metabolome over the measurement time. In lysed fibroblasts and adrenal-cells, metabolism was ongoing over-time, contrary to a stable metabolite content of the lysed-heated cells. Therefore, to minimize metabolome modifications over the measurement time, it is suggested to use cell lysis in combination with heat inactivation for extended HR-MAS NMR measurements.