On Sunday (October 31), a 28-year-old man from Hove was arrested on suspicion of administering poison with intent to injure.
A 19-year-old man from Brighton was arrested on Monday morning (November 1) on suspicion of the same offence.
Both have been bailed while enquiries continue.
Police have received a number of recent reports of people becoming unwell during or after nights out, with some finding puncture marks on their body or believing their drink had been tampered with.
Officers have increased patrols as part of their continued work policing the night-time economy and have been working closely with partners and licensed premises on initiatives to help keep people safe.
These include unannounced license checks at venues, briefings with security staff prior to opening and targeted, visible patrols around bars, clubs and restaurants every night of the week.
Chief Superintendent Justin Burtenshaw, divisional commander for Brighton and Hove, said: “We continue to work around the clock to investigate these troubling reports and will do everything in our power to catch the perpetrators and bring them to justice.
“Please be assured that we take all reports incredibly seriously and ask anybody who believes they may have been a victim to let police or bar staff know as soon as possible so they can be tested before potential drugs leave their system and evidence can be gathered.
“Reports can also be made to police online, via 101 or by dialling 999 in an emergency.”