Small RNAs (sRNAs) that act by base pairing with trans-encoded mRNAs modulate metabolism in response to a variety of environmental stimuli. Here, we describe an Hfq-binding sRNA (FnrS) whose expression is induced upon a shift from aerobic to anaerobic conditions and which acts to downregulate the levels of a variety of mRNAs encoding metabolic enzymes. Anaerobic induction in minimal medium depends strongly on FNR but is also affected by the ArcA and CRP transcription regulators. Whole genome expression analysis showed that the levels of at least 32 mRNAs are downregulated upon FnrS overexpression, 15 of which are predicted to base pair with FnrS by TargetRNA. The sRNA is highly conserved across its entire length in numerous Enterobacteria, and mutational analysis revealed that two separate regions of FnrS base pair with different sets of target mRNAs. The majority of the target genes were previously reported to be downregulated in an FNR-dependent manner but lack recognizable FNR binding sites. We thus suggest that FnrS extends the FNR regulon and increases the efficiency of anaerobic metabolism by repressing the synthesis of enzymes that are not needed under these conditions.