ABSTRACT: While the ‘upside-down’ jellyfish Cassiopea xamachana feeds heterotrophically, its energy requirements are likely met through its symbiosis with the dinoflagellate symbiont Symbiodinium. To investigate the potential coupling of host and symbiont metabolism within C. xamachana, we assessed whether variation in the isotope values (δ¹³C and δ¹⁵N) of photosymbiont-rich oral arm tissue was reflected in bell tissue, which is predominately composed of thick animal mesoglea. Samples were collected from 5 geographically disparate sites, including a site influenced by anthropogenically-derived nutrients. Oral arm δ¹³C values were variable across sites, reflecting varying inputs of marine, terrestrial, and seagrass-derived carbon. Low (<0‰) δ¹⁵N values of oral arm tissue at the 4 non-impacted sites suggests nitrogen derived from nitrogen fixation, while high (~6‰) δ¹⁵N values from the impacted site suggests the assimilation of ¹⁵N-enriched sources like sewage. Oral arm δ¹³C and δ¹⁵N values accounted for ~75 and 25% of the variation in bell δ¹³C and δ¹⁵N values. The translocation of symbiont-derived carbon and nitrogen to the host was also supported by evidence of trophic enrichment, with bell tissue enriched on average by 1.7 and 3.4‰ compared to oral arm tissue for δ¹³C and δ¹⁵N, respectively. These data support the contention that microbial symbionts within Cassiopea are critical to productivity and nutrient cycling in oligotrophic systems, but also raise important questions about whether symbiont metabolism spurs Cassiopea growth and proliferation at sites with chronic anthropogenic nutrient inputs, where higher abundances can have negative effects on local fauna and flora.