Exercise-induced inflammation is a natural response of the body to physical activity, and it plays an essential role in adaptation to and recovery from exercise. However, excessive inflammation may be detrimental to exercise performance and may contribute to degenerative inflammatory conditions such as arthritis in equine athletes. Nitric oxide (NO) is a molecule that is produced in response to inflammation and has been linked to improved adaptation to exercise through its ability to increase blood flow and oxygen delivery. Algae, specifically Spirulina (SP), has marked antioxidant and anti-inflammatory activities in various inflammatory conditions. The current in vitro study was conducted to quantify the effects of SP on cartilage explant responses to induced inflammation with respect to outcomes relevant to degenerative cartilage disease. Cartilage explants from 15 pigs (240 explants in total) were conditioned with a simulated digest of SP before exposure to an inflammatory stimulus with lipopolysaccharide (LPS). Experiments were run under both normoxic and hypoxic conditions to simulate in vivo conditions at rest and during exercise (respectively). Media (90 samples per treatment, 360 samples in total)were analyzed for Viability, Superoxide Dismutase activity (SOD), NO and Glycosaminoglycan (GAG). Data were analyzed using a student's t-test (viability), TukeyHSD and 2-way ANOVA (SOD, NO and GAG) in R. The data is presented as the mean and standard error of the mean (SEM) and a P-value < 0.05 was considered statistically significant. SP had no effect on chondrocyte viability or superoxide dismutase (SOD) activity over the 6-d treatment period (P > 0.05). In normoxic conditions, SP (90 μg/ mL) significantly increased NO production in LPS-stimulated explants (17.45 ± 0.74 to 20.32 ± 1.05 μg/mL), and SP (30 μg/ mL) protected against LPS-induced GAG release (13.27 ± 0.65 to 11.04 ± 0.48 μg/mL). We observed similar results in hypoxic conditions, with SP (30 μg/ mL) increasing LPS-induced NO production (18.62 ± 0.99- 22.72 ± 1.45 μg/mL). This in vitro study demonstrated that SP may be useful in managing inflammation by inducing higher NO and preventing degenerative cartilage damage by lower GAG release in equine athletes.