The Gulf-Coast tick, Amblyomma maculatum, possesses an elaborate set of selenoproteins, which prevent the deleterious effects from oxidative stress that would otherwise occur during feeding. In the current work, we examined the role of selenoprotein K (SelK) and selenoprotein M (SelM) in feeding A. maculatum by bioinformatics, transcriptional gene expression, RNA interference and antioxidant assays. The transcriptional expression of SelK did not vary significantly in salivary glands or midguts throughout the bloodmeal. However, there was a 58-fold increase in transcript levels of SelM in tick midguts. Ticks injected with selK-dsRNA or selM-dsRNA did not reveal any observable differences in egg viability but oviposition was reduced. Surprisingly, salivary antioxidant activity was higher in selenoprotein knockouts compared with controls, which is probably the result of compensatory transcriptional expression of genes involved in combating reactive oxygen species. In fact, quantitative real-time PCR data suggest that the transcriptional expression of catalase increased in ticks injected with selM-double-stranded RNA. Additionally, the transcriptional expression of selN decreased ∼90% in both SelK/SelM knockdowns. These data indicate that SelK and SelM are salivary antioxidants but are not essential for tick survival or reproduction and are compensated by other antioxidant systems.