A new type of micro-osmometer is described in which water absorption of small tissue samples is measured by a quartz crystal microbalance (QCM). The swelling of the sample deposited on the surface of a quartz crystal is determined by monitoring the change in resonance frequency of the quartz sensor as a function of the vapor pressure in the surrounding environment. The measurement principle is verified by studying the water uptake of poly(vinyl alcohol) films. Reasonable agreement is found between the results obtained by the QCM-based osmometer and previous osmotic pressure measurements made on a similar poly(vinyl alcohol) sample. The feasibility of the new method is demonstrated by measuring the osmotic response of tissue-engineered cartilage samples. It is found that the osmotic pressure of cartilage substantially increases with culture time. The present result is consistent with cartilage models, suggesting that the proteoglycan content governs the compressive resistance of the tissue.