Make sure it's necessary. If you're making redundancies for financial reasons, consider your alternatives, such as amending overtime or offering sabbaticals. Remember: losing experience will cost the firm.
Tell the right people, in the right order. The news absolutely has to come from you. Beware the reach of the rumour mill.
Do it properly. Firing people is unpleasant, but it's part of what you're paid for. Don't do a Peter Guild. The furniture firm laid off staff by text, telling them to 'pass it on'. Offer consultation and take people through the process.