The diverse receptors of the C-type lectin superfamily play key roles in innate immunity. In mammals, cell surface receptors with C-type lectin domains are involved in pathogen recognition and in immune response, and in some cases are exploited by pathogens to gain entry into cells. This study reports on sequence and expression analysis of three paralogous group II C-type lectins from the teleost fish Atlantic salmon (Salmo salar). Each of the receptors showed similarity to immune-relevant mammalian receptors in terms of amino acid sequence and overall organization within the C-type lectin-like domain (CTLD). Two of the three have cytoplasmic motifs consistent with the immunoreceptor tyrosine-based activation motifs (ITAM), which are known to modulate downstream functions in leukocytes. All three C-type lectin receptors were expressed in multiple tissues of healthy fish, including peripheral blood leukocytes and salmon head kidney cells (SHK-1). Each receptor was up-regulated in salmon liver in response to infection by Aeromonas salmonicida and one receptor was substantially up-regulated in cultured SHK-1 cells in response to lipopolysaccharide (LPS). Putative binding sites for the CAAT-enhancer-binding protein (C/EBP) family of transcription factors in the regulatory regions of these C-type lectin genes may mediate their response to bacteria and LPS in salmon leukocytes. The identification of these types of receptors in distinct populations of cells within the immune system will provide important markers for identifying and categorizing the state of differentiation or activation of these cells and lead to further understanding of the interaction between the salmon host and multiple pathogens.