Mangroves are highly productive tropical ecosystems influenced by seasonal and daily salinity changes, often exposed to sewage contamination, oil spills and heavy metals, among others. There is limited knowledge of the influence of salinity on the ability of microorganisms to degrade xenobiotic compounds. The aim of this study were to determine the salinity influence on the degradation of xenobiotic compounds in a semi-arid mangrove in La Guajira-Colombia and establish the more abundant genes and degradation pathways. In this study, rhizospheric soil of Avicennia germinans was collected in three points with contrasting salinity (4H, 2 M and 3 L). Total DNA extraction was performed and shotgun sequenced using the Illumina HiSeq technology. We annotated 507,343 reads associated with 21 pathways and detected 193 genes associated with the degradation of xenobiotics using orthologous genes from the KEGG Orthology (KO) database, of which 16 pathways and 113 genes were influenced by salinity. The highest abundances were found in high salinity. The degradation of benzoate showed the highest abundance, followed by the metabolism of the drugs and the degradation of chloroalkane and chloroalkene. The majority of genes were associated with phase I degradation of xenobiotics. The most abundant genes were acetyl-CoA C-acetyltransferase (atoB), catalase-peroxidase (katG) and GMP synthase (glutamine-hydrolysing) (guaA). In conclusion, the metagenomic analysis detected all the degradation pathways of xenobiotics of KEGG and 59% of the genes associated with these pathways were influenced by salinity. Mangroves have the ability to degrade various xenobiotic compounds under different levels of salinity.