As with all cephalopods, but unlike other mollusks, octopuses have a closed circulatory system, where the blood remain inside blood vessels. Octopuses have three hearts; two branchial hearts pump blood through each of the two gills, while the third is a systemic heart that pumps blood through the body. The systemic heart is inactive when the animal is swimming and thus it tires quick and prefers to crawl.

Octopus blood contains the copper-rich protein hemocyanin for transporting oxygen. This makes the blood very viscous, being four times slower than water, and requires consider pressure to flow through the body. As such, octopuses have very high blood pressures, which can exceed 7 mm HG. As with vertebrates, the blood vessels of cephalopods are arteries and can maintain their blood pressure. Although less efficient under normal conditions than the iron-rich hemoglobin of vertebrates, in cold conditions with low oxygen levels, hemocyanin oxygen transportation is more efficient than hemoglobin oxygen transportation. The hemocyanin is dissolved in the plasma instead of being carried within red blood cells, and gives the blood a bluish color.

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