Fast and noninvasive detection of cellular stress is extremely useful for fundamental research and practical applications in medicine and biology. We discovered that light scattering spectroscopy enables us to monitor the transformations in cellular organelles under thermal stress. At the temperatures triggering expression of heat shock proteins, the refractive index of mitochondria increase within 1 min after the onset of heating, indicating enhanced metabolic activity. At higher temperatures and longer exposures, the organelles increase in size. This technique provides an insight into metabolic processes within organelles larger than 50 nm without exogenous staining and opens doors for noninvasive real-time assessment of cellular stress.