ABSTRACTMarine macroalgae are rich in bioactive compounds that can, when consumed, impart beneficial effects on animal and human health. The red seaweedChondrus crispushas been reported to have a wide range of health-promoting activities, such as antitumor and antiviral activities. Using aCaenorhabditis elegansinfection model, we show thatC. crispuswater extract (CCWE) enhances host immunity and suppresses the expression of quorum sensing (QS) and the virulence factors ofPseudomonas aeruginosa(strain PA14). Supplementation of nematode growth medium with CCWE induced the expression ofC. elegansinnate immune genes, such asirg-1,irg-2,F49F1.6,hsf-1,K05D8.5,F56D6.2,C29F3.7,F28D1.3,F38A1.5 ZK6.7,lys-1,spp-1, andabf-1, by more than 2-fold, whileT20G5.7was not affected. Additionally, CCWE suppressed the expression of PA14 QS genes and virulence factors, although it did not affect the growth of the bacteria. These effects correlated with a 28% reduction in the PA14-inflicted killing ofC. elegans. Kappa-carrageenan (K-CGN), a major component of CCWE, was shown to play an important role in the enhancement of host immunity. UsingC. elegansmutants, we identified thatpmk-1,daf-2/daf-16, andskn-1are essential in the K-CGN-induced host immune response. In view of the conservation of innate immune pathways betweenC. elegansand humans, the results of this study suggest that water-soluble components ofC. crispusmay also play a health-promoting role in higher animals and humans.