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Background Giardia has been associated with reduced risk of diarrhea in children in low-resource settings, but the mechanism underlying this association is unknown. To assess whether Giardia may shape colonization or infection with other enteric pathogens and impact associations with diarrhea, we examined Giardia and enteric pathogen codetection among children Methods We tested for Giardia and other enteric pathogens using enzyme-linked immunosorbent assays and real-time polymerase chain reaction (PCR) on stool, respectively. We evaluated associations between Giardia and enteric pathogen detection using multivariable logistic regression models separately for children with moderate-to-severe diarrhea (MSD, cases) and free of diarrhea (controls). Results Among 11 039 enrolled children, Giardia detection was more common among controls (35%) than cases (28%, P < .001). Campylobacter coli/jejuni detection was associated with Giardia in controls in The Gambia (adjusted odds ratio [aOR] [95% confidence interval {CI}]: 1.51 [1.22‒1.86]) and cases across all sites (1.16 [1.00‒1.33]). Among controls, the odds of astrovirus (1.43 [1.05‒1.93]) and Cryptosporidium spp. (1.24 [1.06‒1.46]) detection were higher among children with Giardia. Among cases, the odds of rotavirus detection were lower in children with Giardia in Mali (.45 [.30‒.66]) and Kenya (.31 [.17‒.56]). Conclusions Giardia was prevalent in children