We determined serum biochemistry and hematologic values for island spotted skunks (Spilogale gracilis amphiala) on Santa Cruz Island (California, USA). Samples were collected from island spotted skunks chemically restrained with ketamine hydrochloride and acepromazine in August 1999 (dry season) and from skunks manually restrained in August 2000 (dry season) and January 2001 (wet season). One parameter, glucose, significantly differed with season, with higher levels during the wet season. Serum chemistry and hematologic profiles suggest that method of restraint (manual or chemical), as well as other methodologic details, may influence blood characteristics in the island spotted skunk.