His wife Venetia, a noted beauty, died suddenly in 1633, prompting a famous deathbed portrait by Van Dyck and a eulogy by Ben Jonson. (Digby was later Jonson's literary executor. Jonson's poem about Venetia is now partially lost, because of the loss of the centre sheet of a leaf of papers which held the only copy.) Digby, stricken with grief and the object of enough suspicion for the Crown to order an autopsy (rare at the time) on Venetia's body, secluded himself in Gresham College and attempted to forget his personal woes through scientific experimentation and a return to Catholicism. At Gresham College he held an unofficial post, receiving no payment from the College. Digby, alongside Hungarian chemist Johannes Banfi Hunyades, constructed a laboratory under the lodgings of Gresham Professor of Divinity where the two conducted botanical experiments.
