Lyophilization, or freeze-drying, of pharmaceutical proteins is often the only processing method that provides requisite long-term product stability. Freezing and drying, however, can cause acute damage to proteins. To alleviate damage, formulations frequently include protein stabilizers (often polymers and/or sugars), as well as buffering salts and "inert" bulking agents. While great efforts are placed on developing a formulation and suitable lyophilization cycle, incompatibilities among components through freezing and drying have been almost completely ignored. We demonstrate that solutions of poly(ethylene glycol) (PEG) and dextran, initially below critical concentrations for phase separation, do indeed experience a liquid-liquid phase separation induced by freeze concentration during the lyophilization cycle. The separation is shown to evolve with annealing at -7 degrees C and can be effectively inhibited simply by replacing NaCl with KCl in the formulation buffer. In addition, we show that phase separation causes unfolding of a model protein, recombinant hemoglobin, when freeze-dried in the PEG/dextran system. When the phase separation is averted by switching to KCl, the protein structural damage is also avoided. Measurements of pH in the frozen solutions show that the structural damage is not a result of pH changes. We suggest that KCl forms a glass with rapid cooling which kinetically prevents the phase separation and thus the protein structural damage.