Speaking to the Scottish Parliament Covid-19 recovery committee on Thursday, Mr Yousaf said he and the Scottish Government are aware “just how serious the situation is”.
Mr Yousaf pointed to pressure on social care as well as hospitals, and said he expects flu to be worse than usual after a reduced season last year.
It comes after warnings from unions that staff are dreading winter, with many feeling the strain of long hours and limited breaks.
Unions have also said patient safety may be at risk as staff become more and more overstretched.
Labour MSP Alex Rowley told the committee of staff complaints the nurse-patient ratio is “way beyond what is acceptable” in some situations, and warnings there are times when “hospitals are not safe”.
In response, Mr Yousaf said safety concerns should be raised with health boards and, in turn, the Scottish Government.
“I, and we, the government, have a grasp of just how serious the situation is, across our NHS and social care,” he said.
“I think it's really important not just to talk about the pressure in hospitals. There is significant pressure in our hospitals, but also across social care as well.”
Mr Yousaf said he hoped the extra £300 million announced this week to help the NHS tackle the coming winter would help to improve the situation.
Measures include recruitment of extra staff and a rise in the minimum wage of social care staff, as well as £60m to increase the capacity of care-at-home services.
But he told the committee: “I have to be upfront with the member and with the public. These measures will help to mitigate some of the challenges, but we're still in for an incredibly, incredibly difficult winter.
“Clinicians tell me that their real concern is not just the Covid pressures – we hope to make a significant dent into those as we're controlling transmission – but the flu and other respiratory viruses.
“Our immunity, we suspect, is quite low. Last year the flu wasn't circulating as much due to the lockdown and restrictive measures we were under. The concern is that the immunity of people is low.”