The M6 Southbound was closed between Junction 6 at Birmingham and 4 for the M42 on Monday after a crash involving cars and a horsebox.
At around 2:25pm on 13th August three vehicles collided: a 38 tonne lorry, a white Vauxhall Combo van and a horsebox.
Two people were airlifted to hospital with serious injuries a 49-year-old man from Willenhall, Walsall, who was the driver of the van and a 40-year-old woman from Oswestry, who was the driver of the horsebox.
Both remain in a serious condition in hospital. West Midlands Ambulance Service said they were not in their vehicles at the time of the crash.
The horsebox had been carrying three horses at the time of the collision. One died at the other two were treated at the scene by a local vet.
Police are appealing for any witnesses on the M6 at the time of the collision to get in touch.
In particular they are keen to hear from anyone who saw the Vauxhall Combo van and horsebox before they crashed.
The northbound carriageway of the motorway was re-opened at approximately 8.30pm while the southbound carriageway re-opened at around midnight.