Shear flow alters the rate at which crystals nucleate from solution, yet the underlying mechanisms remain poorly understood. To fill this knowledge gap, we explore the response to shear of dense liquid clusters, which may serve as crystal nucleation precursors. Solutions of the protein lysozyme were sheared in a Couette cell at rates from 0.3 to 200 s(-1) for up to seven hours. The cluster size and total population volume were characterized by dynamic light scattering. We demonstrate that shear rates greater than 10 s(-1) applied for longer than one hour reduce the volume of the cluster population. The likely mechanism of the observed response involves enhanced partial unfolding of the lysozyme molecules, which exposes hydrophobic surfaces between the constituent domains to the aqueous solution. We show that disruption of the intramolecular S-S bridges does not contribute to the mechanism of response to shear. The decrease of the cluster population volume with increasing shear rate or shear time implies that nucleation could be inhibited at moderate shear rates.