Second generation cephalosporins include: cefaclor, cefamandol, cefonicid, cefuroxime, cefprozil, loracarbef, and ceforanide and structurally related agents: cefoxitin, cefmetazole, and cefotetan. These drugs have, in addition to the spectrum of action of first generation compounds, have extended coverage to organisms. Second generation agents are active against gram-positive bacteria than first-generation drugs.

Second generation drugs are not active against or .

Oral second-generation cephalosporins are active against beta-lactamase-producing or Branhamella catarrhalis. These drugs are used primarily to treat , or lower respiratory tract infections caused by these organisms (H. influenzae or Branhamella catarrhalis).

Some second generation drugs, cefoxitin, cefotetan, and cefmetazole, have activity against (including B. fragilis) and may be used in mixed anaerobic infections such as or diverticulitis.
Cefuroxime: effective in treating community-acquired pneumonia (particularly if pneumonia may be caused by beta-lactamase-producing H. influenzae or Klebsiella pneumoniae.