SPX can refer to:
- Sequenced packet exchange, part of the IPX/SPX protocol suite.
- A file extension used for Speex-encoded audio files
- S&P 500 index ticker
- Superphénix, a nuclear power plant
- Small Press Expo, an alternative comics convention
- Sports Performance eXtreme, a sports shoe and clothing brand
- St Pius X College, Sydney, Australia
- St. Pius X Seminary, Roxas City, Philippines
- St. Pius X, the 257th Pope of the Roman Catholic Church.
- SPX Corporation, a Fortune 500 electronics company
- The National Rail code for St Pancras International railway station in Greater London
- The former IATA and FAA code for Houston Gulf Airport