MicroRNAs (miRNAs) are small noncoding RNAs that play key roles in posttranscriptional regulation processes in living cells. In higher vertebrates, miRNAs can modulate host-pathogen interactions by regulating the innate and adaptative immune responses. miRNAs can be found in cells and in different body fluids, such as plasma, serum, urine, and others, and their expression pattern can be altered in a variety of pathophysiological conditions, such as viral and bacterial infection. Infectious salmon anemia virus (ISAV) is the causative agent of infectious salmon anemia (ISA), which mainly affects the species Atlantic salmon, Salmo salar. ISA has caused epidemic outbreaks in most countries that cultivate S. salar. In Chile, ISAV was the cause of one of the biggest salmon crises due to an unexpected and devastating outbreak during 2007–2010. In the present work, we sequenced, identified and quantified miRNAs from plasma of Salmo salar specimens infected with ISAV. Based on initial experimental data derived from small RNA-Seq analysis, a group of differentially expressed (DE) miRNAs from the infected plasma were selected for expression analysis and to identify their mRNA targets specifically related to immune responses. As a result, we identified for the first time miRNAs in the plasma of Salmo salar. From the miRNAs evaluated during the infection course, ssa-miR-122-5p stands out, which was significantly upregulated at all time-points studied. Finally, five of the DE miRNAs, miR-125b-5p, miR-93a-3p, miR-181a-5-3p, miR-125a-2-3p and miR-145-5p, displayed significant relationships with immune system processes based on their mRNA targets.