OBJECTIVES: The old friends hypothesis (OFH) examines connections between the global increase in immunoregulatory diseases (e.g., allergy and autoimmunity) and reduced exposure to immune-priming symbionts like soil-transmitted helminths. Helminth species, however, vary in their effects on hosts and should be considered separately. We examined relationships between species-specific helminth infection and circulating biomarkers of adaptive immune antibodies (total immunoglobulin E [IgE]), systemic inflammation (C-reactive protein [CRP]), and immune regulation (interleukin-6 [IL-6]), among Indigenous Shuar adults. We predicted that STH infection would be (1) associated with higher levels of IgE and (2) lower levels of CRP, with (3) IL-6 driving these associations based on species-specific relationships. METHODS: One hundred and seventeen Shuar adults provided stool and finger-prick blood samples. BCa bootstrap ANCOVA and partial correlation tests examined relationships among infection status (uninfected, Ascaris infected, Trichuris infected, coinfected), control variables (region, sex, age, body mass), and immune biomarkers. RESULTS: On average, coinfected participants had the highest IgE compared to all other groups. Ascaris-infected individuals had, on average, the lowest CRP levels compared to any other group; this was only significant compared to uninfected participants (p < 0.05). Notably, IL-6 was positively correlated with IgE in Ascaris-infected individuals (p < 0.05) and with CRP in Trichuris-infected individuals (p < 0.05), highlighting its role in differentiating between immunoregulation and inflammation based on species-specific infections. CONCLUSIONS: Immune biomarkers varied by infection status: Ascaris infection may downregulate and Trichuris infection may exacerbate systemic inflammation. These preliminary findings suggest that STH species must be considered separately within the OFH.