Perfluorocarbons (PFCs) are noted for their high gas solubility, making them suitable for oxygen delivery in hypoxic conditions. Developing PFC nanoemulsions (PFCe) can overcome the limitations of current blood transfusion systems, which rely on human donations, resulting in a shortage of donors or safety concerns with non-matched blood. Through a systematic screening of various plasma volume expanders (PVEs) as thickeners, we identified a specific thickener that proved enhanced stability. The optimized PFCe containing this thickener exhibits suitable characteristics for intravenous administration, including osmotic pressure, viscosity, and pH. Ongoing investigations into the toxicity of the formulation in cells and mouse models seem to suggest a favorable safety profile. The findings indicate promising potential for this thickened PFCe for delivering oxygen efficiently, paving the way for future clinical applications.