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- "What's the Cavalry packing?"
"If I need a gun I'll take one."
- ―O'Brien and Melinda May
O'Brien is a S.H.I.E.L.D. agent who worked with Phil Coulson and Melinda May during a mission to capture an Inhuman, during which O'Brien and his team were briefly brainwashed. After the capture of Robert Gonzales' S.H.I.E.L.D. base, he was sent to monitor the agent Fitz who expressed a desire to leave S.H.I.E.L.D.. Later he assisted in the attempted killing of Hive. However O'Brien was later caught in a trap and transformed into one of the Primitives with a bomb containing the Absolution Virus.
- "Did you see that room? How'd she take out that many people? I must have been knocked out I can't remember anything."
"The Cavalry went in after all."
- ―O'Brien and Hart
Agent O'Brien was assigned to the case of Eva Belyakov, a gifted individual and Index candidate who was to be evaluated and taken in by S.H.I.E.L.D. before a different government agency could. He traveled to Bahrain under the command of Agent Hart and with Agents Phil Coulson and Melinda May brought in to help. He joined his fellow agents during the mission briefing where they were ordered to bring in Belyakov alive if possible.
O'Brien watched Coulson try to reason with Belyakov and was instructed to make sure a group of locals, who had been put under the coercion of Eva Belyakov's daughter, Katya, did not interfere with the mission. Eva Belyakov caused a large commotion which resulted in O'Brien and the Bahraini men pulling guns out at each other. One man grabbed Katya Belyakov, so O'Brien went with the thugs so the girl would not be hurt. O'Brien became part of Katya's thrall, and answered Coulson's phone call simply telling him to leave them alone.
The rest of the S.H.I.E.L.D. team that went in were put under Katya's power, and O'Brien fought Melinda May with them. They were brought into a room by Katya following the death of her mother, where May shot the girl before she could kill O'Brien and the other agents and brought them out of her trance. O'Brien could not remember any of the events from when he was under Katya's spell; he only remembered seeing all of the dead men on the floor when he regained consciousness, starting rumors about the infamous tale of May's nickname, "The Cavalry".
Battle Against Hive
O'Brien joined the S.H.I.E.L.D. of Director Phil Coulson. He worked in the Operations division. As S.H.I.E.L.D. found the location of the Inhuman Hive, O'Brien, Piper and two other agents volunteered to join Melinda May and Alphonso Mackenzie to kill Hive. Mackenzie briefed the agents about the mission and they used Zephyr One to go to Union City. On Zephyr One, Director Phil Coulson also briefed the team about their mission and asked them to be careful and smart as they were going to be facing an extremely dangerous and unpredictable enemy.
Upon arriving to Union City, May got the information about Hive's location by tricking one of his Inhumans known as Hellfire. As the team went to where they believed Hive currently was, O'Brien asked why Hive had bought a town and not working in the center. They entered the facility where they saw the Kree Orb in action. Coulson ordered the team to get out quickly. As they were out, a Kree Reapers Satellite crashed directly at the facility. O'Brien informed the team that he had found some really big footprints which horrified Piper and himself.
The team followed the Kree Reapers, who killed everyone they encountered, and Piper saw that one of them sensed something in the church. Piper, May and O'Brien entered the church where they saw the Kree and Hive dueling. Eventually, Hive killed the Kree, so Coulson ordered them to attack. After May and O'Brien shoots did not work, Piper shot him with her RPG, but Hive immediately healed. May ordered them to run. They took the injured Mackenzie away from Daisy Johnson and entered the Containment Module and returned to the Playground.
Becoming a Primitive
- "Whens the bloody hanger door going to get closed O'Brien?"
"We've got engineers on it, we had to wait a few days, parts were delayed."
- ―Leo Fitz and O'Brien
Back at the Playground, O'Brien worked alongside Leo Fitz as they oversaw the arrival of some crates being delivered while ensuring that the captured Hive was ready for transportation inside his Suspension Gel. Once this had been approved, O'Brien checked on the new crates while Fitz complained about the hanger door still being broken, to which O'Brien noted the crates were filled with the spare parts they needed.
Just as Fitz was walking away however, he noticed something on the crates and ordered O'Brien to get away. However it was too late as the crates exploded, filling the room with the contaminated Terrigen Mist. O'Brien was suffocated by the Mist and underwent Terrigenesis, transforming him into one of the hideous Primitives. Losing control of his mind, O'Brien forced other S.H.I.E.L.D. agents to be transformed and freed Hive before causing chaos around the base. When the creator of the Primitives, Holden Radcliffe was found, he warned this was irreversible and O'Brien's fate is left unknown.
- Enhanced Strength: As a Primitive, O'Brien possesses adrenaline induced peak human strength and infrared vision.
To be added
- S.H.I.E.L.D. (First Incarnation)
- Hive † - Enemy turned Enthraller
- Eva Belyakov †
- Katya Belyakov † - Former Enthraller
- Kree Reapers †
- S.H.I.E.L.D. (Second Incarnation) - Allies turned Enemies under Coercion
In chronological order:
- Agents of S.H.I.E.L.D.