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Poor quality romantic relationships increase risk for health problems; elevated systemic inflammation is one promising underlying mechanism. This registered report utilized data from three publicly available data sets with large sample sizes (Add Health, MIDUS, NSHAP) to test this possibility. An internal meta‐analysis across all three studies determined that romantic relationship distress was unrelated to inflammation (assessed via C‐reactive protein levels). In addition, this link was not moderated by gender, socioeconomic status (SES), or the combination of gender and SES.