Purpose: Mechanical injury to articular cartilage precipitates post-traumatic osteoarthritis (PTOA), a leading cause of disability. Our group has shown that sublethal mechanical injury leads to pathogenic mitochondrial dysfunction. These changes were prevented by the antioxidant N-acetylcysteine or via mitochondrial complex I inhibition with amobarbital in vivo. In these studies, cell death was exacerbated by atmospheric oxygen (O2) in vitro but not explored further. We wanted to examine the direct effects of hyperoxia upon chondrocyte redox behavior in our large animal osteochondral explant model. We employed carbon monoxide (CO) to disable heme-containing proteins, including many O2 metabolizing systems. We have developed a gas entrapping foam that allows delivery of CO in a controlled fashion, and produces antioxidant and anti-inflammatory effects in rodent models of inflammatory bowel disease. Though CO has long been known as “the silent killer”, it is also a critical gasotransmitter for mitochondrial and redox biology. Upregulation of heme oxygenase-1 (HO-1), an enzyme expressed by chondrocytes that produces CO, is important to PTOA prevention in rodents; however, its normal function is not well understood within the joint. We hypothesize that hyperoxia disturbs primary chondrocyte redox status and exacerbates traumatic injury in a heme-dependent manner.