EMERGENCY services were called to the A16 at Holton Le Clay at 2pm on Wednesday following a road traffic collsion involving a silver Nissan Micra and a silver Peugeot Partner.
The driver of the Nissan was a 720year-old man and his passenger was a 71 year-old woman, both from Cleethorpes.
The driver of the Peugeot, a 71-year-old man, and his 66-year-old female passenger are both from Louth.
All four were taken to Grimsby Hospital with serious injuries.
The 72-year-old driver of the Nissan Micra remains in hospital in Grimsby in a serious condition.
The A16 was closed at the Jug and Bottle junction and, further North, at Waltham Tollbar.
The road was reopened at 7.40pm.
Anyone with information about the incident should contact the Collision Witness Hotline on 01522 558855 or Lincolnshire Police on 0300 111 0300 quoting the incident number.