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Manzoni was appointed Knight Commander of the Order of the Bath (KCB) in the 2020 New Year Honours for public service.

As chief executive of the civil service, Manzoni resigned from his positions at Leyshon Energy and Adamant Ventures but continued to serve as a director for SABMiller, for which he was criticised by MPs including Sarah Wollaston, then a Conservative MP serving as chair of the health select committee, as a conflict of interest given SABMiller's opposition to minimum alcohol pricing. An open letter from medical professionals and charities argued that the director role was incompatible with his civil service role. The Cabinet Office said that it was satisfied that there was no conflict of interest, before later announcing that Manzoni would resign from his position as director in 2015.

In 2015, Manzoni told a conference of the FDA trade union that civil service roles didn't need as much pay as they were more interesting than the private sector. He also described plans to improve collaboration between government departments.

In February 2014, Manzoni joined the British civil service as the chief executive of the Major Projects Authority, a role under the remit of the Cabinet Office. His former BP boss John Browne, who had also left BP in 2007 sat on Manzoni's appointment panel but did not chair it.

On 13 October 2014, Manzoni was appointed as the first chief executive of the civil service, after the position was split out from that of the head of the Home Civil Service when Bob Kerslake retired. A number of business figures who had been approached for the role were reported to have turned it down, with one commenting that the job was "un-doable", and the Financial Times reported that the government had drawn up a "plan B" to appoint Manzoni. His appointment was criticised by the Green Party Member of Parliament (MP) Caroline Lucas.

During his time at Talisman the company focused on shale gas, selling a non-controlling stake in its North Sea business to Sinopec in July 2012. Manzoni resigned from Talisman and was replaced by Hal Kvisle in September 2012. In July 2015, the United States Environmental Protection Agency reported that it had fined Talisman Energy $62,457 for more than fifty health and safety violations at sites in Pennsylvania.

In 2007, a month after the BP report was made public, Manzoni left BP to become the president and chief executive officer of Talisman Energy, an oil and gas exploration and production company. He replaced James Buckee, who had headed the company for 14 years. In his last year working at BP, Manzoni earned a salary of £758,000.

Manzoni was chief executive for refining and marketing at BP at the time of the Texas City Refinery explosion in 2005, in which 15 people were killed and 170 injured. An internal BP investigation cleared him of "serious neglect or intentional misconduct" but said he should have taken more steps to consider and mitigate the risks long before the disaster occurred, and criticised several aspects of his conduct. The company was fined $21m (£13m) for breaching safety rules.

Manzoni studied civil engineering as an undergraduate and a Masters degree in petroleum engineering at Imperial College London. He later studied for a Masters degree in management as a Sloan Fellow at Stanford University in 1994. He also has a Master of Business Administration degree.

Manzoni started to work for the oil and gas company BP in 1983. In 2000, he was a group vice president at the company.

Sir John Alexander Manzoni KCB (born 1960) is a British senior civil servant and business executive, who currently serves as chief executive of the civil service and the Cabinet Office Permanent Secretary.